Vol.:(0123456789)1 3

Archives of Osteoporosis (2021) 16:176 https://doi.org/10.1007/s11657-021-01035-z

ORIGINAL ARTICLE

Consensus evidence‑based clinical practice guidelines for the diagnosis and treat‑to‑target management of osteoporosis in Africa: an initiative by the African Society of Bone Health and Metabolic Bone Diseases

Y El Miedany1,2  · Farhanah Paruk3  · Asgar Kalla4  · A. Adebajo5  · Maha El Gaafary6  · Abdellah El Maghraoui7  · Madeleine Ngandeu8  · Dzifa Dey9  · Naglaa Gadallah10 · Mohamed Elwy10 · Farzana Moosajee11  · Mohammed Hassan  Abu‑Zaid12  · Salwa Galal10  · Soussen Miladi13  · Waleed Hassan14  · Abubaker Fadlelmola15 · Sally Saber10

Received: 25 August 2021 / Accepted: 1 November 2021 © International Osteoporosis Foundation and National Osteoporosis Foundation 2021

AbstractSummary The objective of this consensus statement is to inform the clinical practice communities, research centres and policymakers across Africa of the results of the recommendations for osteoporosis prevention, diagnosis and management. The developed guideline provides state-of-the-art information and presents the conclusions and recommendations of the consensus panel regarding these issues.Purpose To reach an African expert consensus on a treat-to-target strategy, based on current evidence for best practice, for the management of osteoporosis and prevention of fractures.Method A 3-round Delphi process was conducted with 17 osteoporosis experts from different African countries. All rounds were conducted online. In round 1, experts reviewed a list of 21 key clinical questions. In rounds 2 and 3, they rated the statements stratified under each domain for its fit (on a scale of 1–9). After each round, statements were retired, modified or added in view of the experts’ suggestions and the percent agreement was calculated. Statements receiving rates of 7–9 by more than 75% of experts’ votes were considered as achieving consensus.Results The developed guidelines adopted a fracture risk-centric approach. Results of round 1 revealed that of the 21 pro-posed domains, 10 were accepted whereas 11 were amended. In round 2, 32 statements were presented: 2 statements were retired for similarity, 9 statements reached consensus, whereas modifications were suggested for 21 statements. After the 3rd round of rating, the experts came to consensus on the 32 statements. Frequency of high-rate recommendation ranged from 83.33 to 100%. The response rate of the experts was 100%. An algorithm for the osteoporosis management osteoporosis was suggested.Conclusion This study is an important step in setting up a standardised osteoporosis service across the continent. Building a single model that can be applied in standard practice across Africa will enable the clinicians to face the key challenges of managing osteoporosis; furthermore, it highlights the unmet needs for the policymakers responsible for providing bone health care together with and positive outcomes of patients’ care.

Keywords Osteoporosis · Guidelines · Africa · Bisphosphonates · Denosumab · Parathyroid hormone · Romosozumab · FRAX · Falls · African osteoporosis guidelines

Introduction

Osteoporosis is a public health epidemic that has negative impacts on health outcomes together with an enormous eco-nomic burden. The clinical relevance of osteoporosis lies in its associated fragility fractures, especially hip fractures,

* Y El Miedany yasserelmiedany@gmail.com

Extended author information available on the last page of the article

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 2 of 20

and usually it is a silent disease until such an event occurs [1]. Worldwide, osteoporosis causes more than 9 million fractures a year, meaning that there is a fragility fracture every 3 s [2]. In the Western World, it is estimated that about 1 in 3 women and 1 in 5 men above the age of 50 years old will sustain a fracture during their remaining lifetime [3]. After the age of 50 years, most sites of fracture can be considered characteristic locations of osteoporosis. Hip and vertebral fractures are the most common and serious osteo-porotic fractures. Other fragility fractures, particularly in women, such as those of the humerus, forearm, ribs, pelvis and tibia (but not including ankle fractures), after the age of 50 years, have been reported to be associated with low bone mineral density (BMD) [4]. The direct annual cost of treat-ing osteoporotic fractures of people on average is reported to be between 5000 and 6500 billion US Dollars in Canada, Europe and the USA alone, not considering indirect costs such as disability and loss of productivity [5]. Therefore, prevention of this disease can significantly reduce the mor-bidity, mortality and costs incurred by the health system.

Across Africa, the issue of bone health continues to be a major challenge. Osteoporosis has been overlooked as a health care priority in Africa, particularly in the sub-Saharan region [6]. This has been linked to several reasons. Firstly, health authorities have been overwhelmed by the burden of communicable diseases such as tuberculosis and human immunodeficiency virus (HIV) [7]. Secondly, tools to assess the BMD and consequently diagnose osteoporosis such as dual X-ray absorptiometry (DXA) are not widely available, hindering early diagnosis and treatment of the disease. Fur-thermore, concerns regarding inadequate calcium intake dur-ing adolescent years, low body mass index, prolonged dura-tion of lactation amongst women during childbearing years, low levels of vitamin D and physical inactivity amongst Africans are all risk factors for osteoporosis [8].

On another front, the demographic changes taking place in Africa have fuelled both the diagnostic and therapeutic osteoporosis inertia in Africa. Census reports showed that both the total population size and life expectancy in Africa have increased significantly in the last two decades. An overview of demographic ageing in Africa published by the United Nations [9] found that Africa will have the fastest growth rate of older adults compared to any other region in the world. Between 2020 and 2050, the older African population is projected to triple from 74.4 million to 235.1 million and will outpace that of any other region of the world [10]. This has been supported by the new Census report on ageing trends in Africa [11] which revealed that between 2017 and 2050, 50% of the world’s population is expected to be in 9 countries (India, Nigeria, Democratic Republic of the Congo, Pakistan, Ethiopia, United Republic of Tanzania, United States of America (USA), Uganda and Indonesia), i.e. 5 of them are African nations.

African older adults play critical economic, family and community roles. Studies show that majority of the adults aged 60 to 64 years and around half of those aged 65 years and older in Africa remain in the labour force. Many older Africans, particularly women, contribute substan-tial amounts to providing unpaid home and care work [9]. Therefore, caring for this sector of the population become a priori. So far, there have not been any guidelines or treat-ment recommendations published for the management of osteoporosis in Africa. This guideline has been developed as an initiative by the African Society of Bone Health and Metabolic Diseases (ASBoM) with the intention of reduc-ing the risk of osteoporosis-related fractures and thereby maintaining the quality of life for African people living with osteoporosis. It has been based on the outcomes of systematic reviews carried out in Africa on epidemiology of osteoporotic fractures as well as risk factors of osteo-porosis in Africa. The objective is to provide a consensus, evidence-based information about the diagnosis, evaluation and treat-to-target management of osteoporosis in both men and postmenopausal women for the African health care pro-fessionals managing osteoporosis patients in general, regu-latory bodies, health-related organizations and interested patients’ groups/laypersons. Although framed for Africa, it is hoped that these guidelines will be valuable for bone health specialists across the globe.

Methods

A qualitative synthesis of scientific evidence and consensus, based on clinical experience and existing scientific evidence, was used to formulate the study design and the following procedures. This work conforms to the preferred reporting items for systematic reviews and meta-analyses guidelines for reporting systematic reviews [12].

Study teams

Core team Core team was composed of four experts in bone metabolism who were selected by the African Society of Bone Health and Metabolic Bone Diseases. Their task was to supervise, coordinate and assist with developing the scope of the project and initial Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions. The core team prespecified outcomes as critical for each PICO ques-tion for the systematic literature review. The team also nomi-nated the expert panel and drafting the manuscript.

Literature review team

Led by an experienced literature review consultant and based on specific research questions identified to focus on

Archives of Osteoporosis (2021) 16:176

1 3

Page 3 of 20 176

the treat-to-Target management of osteoporosis, the litera-ture review was conducted with the assistance of an expert in methodology. The team completed the literature search (the PubMed/ MEDLINE, EMBASE and Cochrane data-bases), data abstraction and the quality of evidence rating [13]. Following the revision, each of the experts respon-sible for the literature review provided recommendations regarding each section based on evidence, when that was available or on their own experience. The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system (Table 1) [14].

Data sources and search strategies

The PICO questions (Table 2) were used to conduct the liter-ature search in PubMed, Embase and Cochrane Library data-bases. Literature search strategies were carried out to locate randomised clinical trials evaluating the efficacy of osteopo-rosis quality improvement strategies published from 1990 to April 2021. The language was limited to English and French for pragmatic reasons. The search strategies were designed to be broad to have high sensitivity for identifying relevant literature. We used the following Medical Subject Headings (MeSH) terms: osteoporosis, postmenopausal osteoporosis, osteop?nia, T-score, bone resorption, fracture, osteoporosis

Table 1 Levels of evidence and grades of recommendation

Level of evidence

1 Systematic review of all relevant randomised clinical trials or n-of-1 trials2 Randomised trial or observational study with dramatic effect3 Non-randomised controlled cohort/follow-up study (observational)4 Case series, case–control study or historically controlled study5 Mechanism-based reasoning (expert opinion, based on physiology, animal or

laboratory studies)Grades of recommendationA Consistent level 1 studiesB Consistent level 2 or 3 studies, or extrapolations from level 1 studiesC Level 4 studies, or extrapolations from level 2 or 3 studiesD Level 5 evidence or troubling, inconsistent or inconclusive studies of any level

Table 2 Key questions used to develop the guideline 1 Who are the targeted people for these guidelines?

2 What are the fracture risk factors?3 How to assess for fracture risk and what are the cut-off points?4 How is osteoporosis diagnosed?5 When osteoporosis is diagnosed, what is the approach for an appropriate evaluation?6 What are the fundamental non-pharmacologic measures recommended for optimum bone health?7 Who is in need for pharmacologic therapy?8 What medication should be used to treat osteoporosis?9 What is the approach for osteoporosis pharmacological management?10 What are the recommendations for calcium and vitamin D supplement therapy?11 How is treatment monitored?12 Treat-to-target: What are the targets that reflect successful osteoporosis management?13 How long should patients be treated?14 Is there an opportunity for a drug holiday?15 What is the role of concomitant use of therapeutic agents?16 What is the role of sequential use of therapeutic agents?17 What is the role of vertebral augmentation for compression fractures?18 What is the importance of falls assessment?19 How important is the implementation of fracture liaison service (FLS)?20 How osteoporosis in men is managed?21 How to manage the patients on glucocorticoids therapy?22 What is the advice given to osteoporosis patients during the COVID-19 pandemic?

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 4 of 20

treatment, osteoporosis management, calcium, vitamin D, alendronate, risedronate, etidronate, ibandronate, zoledronic acid, raloxifene, calcitonin, teriparatide, hormone replace-ment therapy, teriparatide, abaloparatide, romosozumab, denosumab, glucocorticoids, treatment induced osteopo-rosis, hip protectors, meta-analysis, systematic reviews, randomized controlled trials, bone density, FRAX, fracture liaison service, falls, Covid-19, treat to target. Keywords used were dependent on the PICO elements used in differ-ent combinations. Literature searches on 23rd April 2021 for PubMed and Cochrane Library databases, and on 28th April 2021 for Embase. Duplicate screening of literature search results was performed electronically. Additional rel-evant studies were retrieved by reviewing the reference lists of studies identified with the database search strategies that met the inclusion criteria.

Study selection

We selected relevant studies by applying inclusion and exclusion criteria to the literature retrieved with the search strategies.

Inclusion criteria

Articles included were systematic reviews, randomised controlled trials (RCTs), uncontrolled trials, observational studies including cohort, case–control and cross-sectional studies, or those where economic evaluation was made.

Exclusion criteria

Editorials, commentaries, conference abstracts and non-evidence-based narrative/personal reviews were excluded.

Expert panel Given the fact that the developed guideline will be adopted across the continent of Africa, it was vital that the participating expert panel involved in developing the guideline would include experts from all the African conti-nent regions (Central, North, West, East and South Africa). Expert panel members were appointed by the core team. The core leadership team nominated 17 participants. The criteria for their selection included existence of professional knowl-edge and experience (at least 8 years of experience) in the field of bone health, management of osteoporosis and active participation in scientific research on bone health disorders. The expert panel assisted with developing the scope of the project and refining the PICO questions. PICO questions were drafted into recommendation statements and were sent to the expert panel with the evidence report who voted on the recommendations.

Key questions used to develop the guideline

This guideline was based on a series of structured key questions that define the targeted population, frac-ture assessment, diagnostic tools, investigation, the comparison(s) utilised and the outcomes used to measure efficacy, effectiveness or risk. The evidence to answer the clinical questions was collected according to the follow-ing steps: formulation of clinical questions, structuring of questions, search for evidence, critical evaluation and selection of evidence, presentation of results and recom-mendations. These questions, shown in Table 2, formed the basis of the systematic literature search and conse-quently the clinical care standards.

Developing the standards of clinical care framework

Based on the answers to the structured key questions and the literature review, a structured template was devel-oped to facilitate standardised identification of guideline components. For each guideline component, the format in which the recommendations/information was provided and extracted has been identified.

Delphi process

The Delphi technique is a structured method widely used to gather important information on a specific topic. It relies on the key assumption that forecasts from a group are generally more accurate than those from individuals. Therefore, the aim of the Delphi method is to construct consensus forecasts from a group of experts in a structured iterative manner. Its methodology is based on a series of questionnaires or ‘rounds’ addressed to experts. The key features of this method are the anonymity of participants and controlled feedback [15].

Delphi rounds

This was based on a three-stage on-line survey.

– The first round: the participants were asked to consider the items identified by the systematic literature review, to suggest new items that might have been missed and to clarify items that might be unclear.

– The second round was based on the results of the first round, and participants were asked to rate each item from 1 (not appropriate) to 9 (completely appropriate) and give their comments.

– The third round, the participants reviewed the responses to each item obtained in the second round, after amend-

Archives of Osteoporosis (2021) 16:176

1 3

Page 5 of 20 176

ments wherever appropriate, and to rate the items after alterations (from 1 to 9)

Voting process

Live online-delivered voting was carried out in repeated rounds that were strictly time limited. All members of the task force were invited to participate and pre-informed of the time of opening and closure of each round of votes. Unique access links were sent out, and anonymous votes were gath-ered and processed. Comments on re-phrasing, potential ambiguity and unidentified overlaps were gathered regard-ing each statement at the same time in the voting process. Only the members of the task force had the right to vote on the statements.

Rating

Each statement is rated between 1 and 9 where 1 being ‘complete disagreement’ and 9 being ‘complete agreement’. Generally, 1–3, 4–6 and 7–9 represent disagreement, uncer-tainty and agreement, respectively. The ‘uncertainty’ vote represents ‘inconvenience about the accuracy of the recom-mendation’. There was no requirement to vote on all state-ments, and the members were encouraged to abstain if they felt that a statement fell outside their area of expertise. All statements were allowed for the entry of comments, which were reviewed by the scientific committee after each round of voting. The same scenario was adopted in each round of votes; the members were further urged to leave comments wherever they vote a disagreement. This enabled the panel to identify an instance of misinterpretation of statement and invalidate the vote on that statement.

Definition of consensus

Definition of consensus was established before data analy-ses. It was determined that consensus would be achieved if at least 75% of participants reached agreement (score 7–9) or disagreement (score 1–3) [15–18]. A statement was retired if it had a mean vote below 3 or a ‘low’ level of agreement. Statements whose rate come in the uncertainty score (4–6) were revised in view of the comments. The levels of agree-ment on each statement of recommendation were defined as ‘high’ if after the second round of votes, all votes on a state-ment fell into the agreement bracket (7–9) [18].

Data management and analysis

Survey data were combined as a total sample, included 17 individual responses, were analysed using SPSS Statistical Software (Statistical Package of Social Science, Armonk, New York), and results reported as means and standard

deviation. Analysis by geography was not possible due to the anonymity of survey responses.

Ethical aspects

This study was performed in accordance with the Helsinki Declaration. Ethics approval was deemed unnecessary. Ver-bal informed consent was required from all the participants included in the study. All the participants were kept anony-mous, in compliance with data protection regulations. The research questions, project oversight and resulting consen-sus-based practice guidelines were created by the core team and expert panel. The resulting guidelines do not reference or recommend any specific product; rather, they focus on how to assess and utilise the evidence to put a frame that is best suited for the patients’ management.

Results

Literature research and evidence selection

Evidence was obtained through literature searches and 3443 potentially relevant studies were initially identified. A total of 3339 studies were excluded for duplication (1266) or by screening of title and abstracts (2073). These are the studies which did not examine population or intervention of inter-est, did not match study design of interest or did not report outcome measures of interest. Therefore, relevant 104 stud-ies were included for full article review. In total, 78 studies were excluded as citations did not provide evidence match-ing a PICO. Therefore, 26 studies were included in this work (Fig. 1).

Expert panel characteristics

The Delphi form was sent to the expert panel (n = 17), who participated in the three rounds. Respondents were drawn from several countries covering the different geographical regions of Africa: Egypt: 8 (47%), Morocco: 1 (5.8%), South Africa: 3 (17.64%) and 1 (5.8%), from each of: Cameron, Nigeria, Ghana, Tunisia and Sudan. The participants were rheumatologists who are specialised in the management of osteoporosis with mean experience of 20.3 ± 11.24 years.

Delphi round 1

The key clinical question comprised of 22 questions. In this round, the participants were asked to rate the overall principles considered in the decision-making for treat-to-target management of patients living with osteoporosis. The response rate for round 1 was 100% (17/17). The 17 experts accepted 10 of the proposed domains, suggested

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 6 of 20

amendments for the remaining 12. Of the suggested changes, comments were raised regarding the domain ‘who are tar-geted in this guideline’, particularly regarding definite dis-crimination of both male and female osteoporosis; hence, it was considered when formulating the statements. There was a diversity of comments whether to merge the statements on treatment duration and the drug holiday, but it was decided to keep them separate. Other comments suggested the strati-fication of osteoporosis management into pharmacological and non-pharmacological with recommendation to clarify the concomitant use of therapeutic agents and adjunctive therapy; hence, a new subheading was added. Some of the modifications consisted of minor wording changes. Table 3 shows a list of the major as well as minor osteoporosis risk factors.

Delphi round 2

Based on input from round 1, the 17 experts were pre-sented with 32 statements stratified under 22 domains. The response rate for round 2 was 100% (17/17). Of the state-ments presented, two statements were retired for similar-ity with another statement, 9 statements reached consensus (i.e. ≥ 75% of respondents strongly agreed or agreed) and

were retained, whereas modifications were suggested for 21 statements. Comments (excluding minor editing sug-gestions) were more frequent for 4 domains: osteoporosis fracture risk, non-pharmacologic measures for bone health, male osteoporosis and steroid-associated osteoporosis. The statements were revised and amended. In addition, one state-ment was suggested to be added to the daily supplementa-tion of calcium and vitamin D therapy domain and another one was added to the non-pharmacologic measures of bone health domain.

Delphi round 3

Based on input from round 2, the 17 experts were pre-sented with 32 statements stratified under 22 domains. The response rate for round 3 was 100% (17/17). The experts came to consensus on the 32 statement to retain in the treat-to-target management guideline. The core team reviewed and made minor revisions to one of the retained statements that reached consensus. Consensus was reached (i.e. ≥ 75% of respondents strongly agreed or agreed) on all the clinical standards. Frequency of high-rate recommendation (rank 7–9) ranged from 83.33 to 100%. The experts were com-fortable with the final list of the statements and with the Delphi process overall. Table 4 shows the level of evidence and grade of recommendation assigned to each statement, in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM) criteria as well as mean ± standard devia-tion and level of agreement [14]. Agreement was unanimous (> 80% agreement) for the wording of the statements.

Recommendations for management of osteoporosis

At the end of round 3, a total of twenty-two domains were obtained and a consensus was reached on all the statements developed. As health care professionals need information that is clear and readily accessible as well as applicable in standard clinical practice, it was important to articulate the developed osteoporosis guideline for the day-to-day prac-tice. This is summarised in Fig. 2 which shows an algo-rithm for the treat-to-target management of postmenopausal osteoporosis.

Discussion

The prevalence of osteoporosis is increasing steadily in developing countries secondary to increased longevity, with osteoporosis and its consequent fractures are becom-ing a major public health issue [21]. Epidemiological studies showed that in sub-Saharan Africa, the prevalence of osteo-porosis was 20reported to range from 18.2 to 65.8% across a heterogenous at-risk population. Similar figures were

Abstract and full text ar�cles from

Pubmed, Scopus & Google scholar

N= 34433339 were excluded by screening of

�tle and abstracts (studies did not

examine popula�on or interven�on

of interest, did not match study

design of interest, or did not report

outcome measures of interest).

N=104 ar�cles remained

78 studies were excluded as

cita�ons did not provide

evidence matching a PICO

N=26 ar�cles remained

Fig. 1 Flow chart for the study selection process

Archives of Osteoporosis (2021) 16:176

1 3

Page 7 of 20 176

reported in North Africa. The prevalence of osteoporosis in Egypt was 21.9% in men and 28.4% in women; whilst 26% of men and 53.9% of women having osteopenia [22]. The prevalence of osteoporosis in Moroccan postmenopau-sal women ranged between 21 and 31% [23, 24], which is similar to Tunisia, where 25% of postmenopausal women have osteoporosis [25], whereas the rate was slightly higher (35.8%) amongst Algerian women [26]. These rates were in concordance with the outcomes of studies evaluating the major clinical consequences of osteoporosis, i.e. fractures. A recent study investigating the incidence of hip fractures amongst Black South Africans found an age-adjusted hip fracture rate of 69.2 per 100,000 per annum and 73.1 per 100,000 per annum for women and men, respectively [27]. This evidence challenges the long-held view that osteoporo-sis-related fractures are rare in Blacks [28, 29] and highlight the importance of addressing the issue of osteoporosis in Africa.

The developed guideline agrees with the published guide-lines from individual African nations for the management of osteoporosis including Egypt [30] and South Africa [31] as well as the international guidelines [32–34]. The guide-line recommends very early intervention with osteoanabolic agents, for patients who are at very high risk of fracture. This agrees with the most recently published treatment

recommendations, which endorsed the sequential as well as switch approaches of therapy [35, 36]. It also advocated a preventive approach for osteopenia patients at moderate to high risk of fractures, which agree with the recent avail-able evidence [20]. The statements on osteoporosis manage-ment for patients with COVID-19 agree with those recently published by the National Osteoporosis Foundation [37]. This highlights the importance of having updated recom-mendations for osteoporosis management based on up-to-date evidence for best clinical practice. This guideline not only provides solutions for early identification of the cases, which will consequently help to will reduce fracture rates, but also enables health care professionals with special inter-est in bone health to face the key challenges of managing osteoporosis in Africa. The guidelines will assist the poli-cymakers responsible for providing care for populations in relation to bone health to formulate appropriate policies.

Either a BMD-centric or a fracture risk-centric approach could be adopted to identify patients for whom pharmaco-logical intervention should be considered. This guideline adopted the fracture risk-centric approach, though the BMD measurement was integrated, mainly for those with moder-ate fracture risk. This was based on the finding that DXA studies are seldomly used in Africa to assess for osteoporosis risk. This has been attributed in several cases to the lack of

Table 3 Modifiable and non-modifiable osteoporosis risk factors

RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; DMPA, depot medroxyprogesterone acetate; GnRH, gonadotropin-releasing hormone; PPIs, proton pump inhibitors; TZD, thiazolidinediones

Non-modifiable risk factors Previous fractureParental history of osteoporosisHistory of early menopause (below age of 45 years)

Modifiable risk factors Low BMI (< 20 kg/m2)SmokingLow bone mineral densityAlcohol intake

Co-existing diseases DiabetesInflammatory rheumatic diseases (RA or SLE)Inflammatory bowel disease and malabsorptionInstitutionalised patients with epilepsyHuman immunodeficiency virusPrimary hyperparathyroidism and endocrine

diseasesChronic liver diseaseNeurological diseases (including Alzheimer’s

disease, Parkinson’s disease, multiple sclerosis, stroke)

Moderate to severe chronic kidney diseaseAsthma

Drug therapy Long-term antidepressantsAntiepilepticsAromatase inhibitorsLong-term DMPAGnRH agonists (in men with prostate cancer)PPIsOral glucocorticoidsTZDs

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 8 of 20

Tabl

e 4

Bre

akdo

wn

of st

atem

ents

of r

ecom

men

datio

ns, i

ts in

divi

dual

rank

by

expe

rt op

inio

n an

d le

vel o

f agr

eem

ent

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

Who

are

targ

eted

in th

ese

guid

elin

es?

Wom

en*P

ostm

enop

ausa

l wom

en a

ged ≥

50 y

ears

(2a)

Postm

enop

ausa

l wom

en a

t hig

h ris

k of

frac

ture

s (2a

)Po

stmen

opau

sal w

omen

who

hav

e ex

perie

nced

a re

cent

frac

ture

(2a)

Wom

en w

ith se

cond

ary

caus

es o

f oste

opor

osis

(2a)

Men

with

a T

scor

e in

the

oste

open

ic ra

nge

(T sc

ore −

1 to

− 2.

5) if

they

hav

e be

en id

entifi

ed to

hav

e a

high

or v

ery

high

frac

ture

risk

(2b)

Men

:- M

en a

t the

age

of 7

0 ye

ars o

r old

er (2

a)- M

en w

hose

age

is le

ss th

an 7

0 ye

ars o

ld, a

t hig

h ris

k of

frac

ture

(2a)

- Men

Ove

r 60 

year

s old

who

hav

e ex

perie

nced

a re

cent

frac

ture

(2a)

- Men

with

seco

ndar

y ca

uses

of o

steop

oros

is (2

a)- M

en w

ith a

T sc

ore

in th

e os

teop

enic

rang

e (T

scor

e − 1

to −

2.5)

if th

ey h

ave

been

iden

tified

to h

ave

a hi

gh o

r ver

y hi

gh fr

actu

re ri

sk (2

b)

2 2 2 2 2 2 2 2 2 2

A A A A B A A A A B

8.9

0.5

94.1

%H

Wha

t are

the

oste

opor

osis

fr

actu

re ri

sk fa

ctor

s?Se

e Ta

ble 

32

A8.

671.

2581

.66

H

How

to a

sses

s for

frac

ture

risk

?an

dw

hat a

re th

e cu

t-off

poin

ts?

• Sc

reen

ing

for f

ract

ure

risk:

- FR

AX

, with

out B

MD

, is a

n im

porta

nt w

eb-b

ased

tool

in th

e as

sess

men

t of f

ragi

lity

frac

ture

risk

in

oste

opor

osis

and

shou

ld b

e us

ed to

scre

en th

e pa

tient

s and

stra

tify

them

acc

ordi

ng to

thei

r fra

ctur

e ris

k- C

onsi

der b

one

min

eral

den

sity

testi

ng b

ased

on

clin

ical

frac

ture

risk

pro

file

- It i

s adv

isab

le to

cal

cula

te th

e FR

AX

scor

e ac

cord

ing

to th

e va

lidat

ed n

atio

nal m

easu

res

- If n

o na

tiona

l mea

sure

s are

avai

labl

e, th

e FR

AX

can

be

calc

ulat

ed a

ccor

ding

to re

gion

al v

alid

ated

m

easu

res

- Adj

ustm

ent o

f the

con

vent

iona

l FR

AX

esti

mat

es o

f pro

babi

litie

s of h

ip fr

actu

re a

nd a

maj

or o

steo-

poro

tic fr

actu

re sh

ould

be

carr

ied

out t

o m

odul

ate

the

risk

asse

ssm

ent w

hene

ver a

ppro

pria

te- W

here

ver p

ossi

ble,

FR

AX

shou

ld b

e ad

juste

d fo

r TB

S (tr

abec

ular

bon

e sc

ore)

- Pat

ient

s sho

uld

be st

ratifi

ed a

ccor

ding

to th

eir r

isk

of fr

actu

re, l

ow, m

oder

ate,

hig

h an

d ve

ry h

igh

risk

Low

risk

incl

udes

no

prio

r hip

or s

pine

frac

ture

s, a

BM

D T

scor

e at

the

hip

and

spin

e bo

th a

bove

− 1.

0 an

d 10

-yea

r hip

frac

ture

risk

< 1%

and

10-

year

risk

of m

ajor

oste

opor

otic

frac

ture

s < 10

%M

oder

ate

risk

incl

udes

no

prio

r hip

or s

pine

frac

ture

s, a

BM

D T

-sco

re a

t the

hip

and

spin

e bo

th

betw

een

– 1

and −

2.5

or 1

0-ye

ar h

ip fr

actu

re ri

sk <

3% o

r ris

k of

maj

or o

steop

orot

ic fr

actu

res <

20%

Hig

h ris

k in

clud

es a

prio

r spi

ne o

r hip

frac

ture

, or a

BM

D T

scor

e at

the

hip

or sp

ine

of −

2.5

or b

elow

or

10-

year

hip

frac

ture

risk

> 3%

or r

isk

of m

ajor

oste

opor

otic

frac

ture

risk

> 20

%Ve

ry h

igh

frac

ture

risk

incl

udes

rece

nt fr

actu

re (e

.g. w

ithin

pre

cedi

ng 1

2 m

onth

s), f

ract

ure

whi

lst

on a

nti-o

steop

oros

is m

edic

atio

n, m

ultip

le fr

actu

res,

frac

ture

s whi

lst ta

king

dru

gs th

at a

ffect

bon

e ad

vers

ely

(e.g

. lon

g-te

rm g

luco

corti

coid

ther

apy)

, a B

MD

T-s

core

≤ −

3, h

igh

risk

of fa

lls o

r pre

vi-

ous h

istor

y of

inju

rious

falls

and

a v

ery

high

frac

ture

pro

babi

lity

(the

exam

ple

give

n is

a F

RA

X

scor

e > 30

% fo

r maj

or o

steop

orot

ic fr

actu

re a

nd >

4.6%

for h

ip fr

actu

re)

Adj

ustm

ent o

f FR

AX

10-

year

pro

babi

lity

of fr

actu

re sh

ould

be

carr

ied

out f

or a

ll pa

tient

s tak

ing

gluc

o-co

rtico

id th

erap

y. T

he in

divi

dual

pat

ient

’s ri

sk sh

ould

be

adju

sted

for t

he g

luco

corti

coid

dos

e [1

9]

1 2A A

8.9

0.5

94.1

Archives of Osteoporosis (2021) 16:176

1 3

Page 9 of 20 176

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

How

is o

steop

oros

is d

iagn

osed

?- B

MD

testi

ng is

the

gold

stan

dard

in d

iagn

osin

g os

teop

oros

is. T

he W

HO

reco

mm

ende

d th

e di

agno

sis

of o

steop

oros

is b

ased

on

the

T-sc

ores

at e

ither

hip

or s

pine

- The

1/3

radi

us m

ay b

e co

nsid

ered

as a

n al

tern

ate

site

whe

n th

e lu

mba

r spi

ne/h

ip is

not

eva

luab

le o

r as

an a

dditi

onal

site

in p

atie

nts w

ith p

rimar

y hy

perp

arat

hyro

idis

m:

Cut

-off

poin

ts o

f T-s

core

:- T

-sco

re ≥

− 1

indi

cate

s nor

mal

BM

D- T

-sco

re b

etw

een −

1 an

d − 2.

5 in

dica

tes o

steop

enia

or l

ow b

one

mas

s- T

-sco

re ≤

− 2.

5 in

dica

tes o

steop

oros

is- T

-sco

re ≤

− 2.

5 ac

com

pani

ed b

y a

frag

ility

frac

ture

den

otes

seve

re o

steop

oros

is- W

hen

the

initi

al d

iagn

osis

of o

steop

oros

is is

mad

e ba

sed

on a

T-s

core

of −

2.5

or b

elow

, the

dia

gnos

is

of o

steop

oros

is re

mai

ns e

ven

whe

n a

subs

eque

nt D

XA

ass

essm

ent s

how

s a T

-sco

re b

ette

r tha

n − 2.

5 (g

rade

2a)

- Oste

opor

osis

can

be

diag

nose

d in

pat

ient

s with

a T

-sco

re b

etw

een −

1.0

and −

2.5

and

incr

ease

d fr

actu

re ri

sk u

sing

FR

AX

® o

r sus

tain

a fr

agili

ty fr

actu

re- T

he d

iagn

ostic

DX

A c

riter

ia e

stab

lishe

d by

the

WH

O a

pply

onl

y to

the

axia

l mea

sure

men

ts (i

.e. l

um-

bar s

pine

, fem

oral

nec

k an

d to

tal h

ip) a

nd d

istal

1/3

of t

he ra

dius

. Thu

s, ot

her t

echn

olog

ies s

houl

d no

t be

used

to d

iagn

ose

oste

opor

osis

but

may

be

used

to a

sses

s fra

ctur

e ris

k

2A

8.58

0.82

100

H

Whe

n os

teop

oros

is is

dia

g-no

sed,

wha

t is t

he a

ppro

ach

for a

n ap

prop

riate

eva

luat

ion?

Hei

ght s

houl

d be

mea

sure

d ev

ery

1–2 

year

s in

adul

ts ≥

50 y

ears

of a

ge- A

sses

s for

cau

ses o

f sec

onda

ry o

steop

oros

isB

ioch

emic

al te

sts:

Bon

e pr

ofile

: cal

cium

, pho

spho

rous

, alk

alin

e ph

osph

atas

e, e

GFR

, cre

atin

ine

Whe

neve

r ind

icat

ed:

- 25-

hydr

oxyv

itam

in D

: sym

ptom

s of v

itam

in D

defi

cien

cy- P

arat

hyro

id h

orm

one

(PTH

): pe

rsist

ent h

yper

calc

aem

ia- S

erum

testo

stero

ne, L

H, F

SH a

nd S

HB

G, P

SA (m

en)

- 24-

h ur

inar

y co

rtiso

l/dex

amet

haso

ne su

ppre

ssio

n te

st- E

ndom

ysia

l and

/or t

issu

e tra

nsgl

utam

inas

e an

tibod

ies (

coel

iac

dise

ase)

Rad

iolo

gica

l:A

sses

smen

t for

pre

senc

e of

ver

tebr

al fr

actu

re(s

) eith

er b

y:- X

-ray

,- D

XA

-bas

ed V

erte

bral

frac

ture

ass

essm

ent (

VFA

) or

- Oth

er ra

diol

ogic

al in

vesti

gatio

ns su

ch a

s CT

or M

RI a

re o

f val

ue p

artic

ular

ly fo

r ver

tebr

al fr

actu

re

asse

ssm

ent

2A

8.83

110

0H

Wha

t are

the

fund

amen

tal n

on-

phar

mac

olog

ic m

easu

res f

or

bone

hea

lth?

- Pat

ient

edu

catio

n/gr

oup

ther

apy

can

be o

f val

ue in

oste

opor

osis

man

agem

ent

- Sha

red

deci

sion

-mak

ing

tool

s are

a g

ood

and

pref

erab

le o

ptio

n to

ens

ure

patie

nt a

dher

ence

to th

erap

y an

d po

sitiv

e tre

atm

ent o

utco

mes

- Life

style

mea

sure

s suc

h as

incr

easi

ng le

vels

of p

hysi

cal a

ctiv

ity a

nd p

erfo

rm w

eigh

t-bea

ring

exer

cise

, sto

p sm

okin

g an

d al

coho

l int

ake,

car

e fo

r oth

er re

leva

nt c

omor

bidi

ties a

s ren

al o

r isc

haem

ic c

ardi

o-va

scul

ar d

isea

ses a

re v

ery

impo

rtant

in im

prov

ing

bone

hea

lth- E

xerc

ise

is im

porta

nt fo

r man

agin

g os

teop

oros

is, w

ith a

ppro

pria

te sa

fety

pre

caut

ions

- Cou

nsel

pat

ient

s to

limit

alco

hol i

ntak

e to

no

mor

e th

an 2

uni

ts p

er d

ay- P

re-tr

eatm

ent d

enta

l che

ck-u

p is

adv

ised

par

ticul

arly

in th

e pr

esen

ce o

f ris

k fa

ctor

s suc

h as

dia

bete

s m

ellit

us o

r hist

ory

of p

oor d

enta

l hea

lth st

atus

- Pre

vent

ion

of fa

lls a

nd c

onsi

der h

ip p

rote

ctor

s

2A

8.9

0.14

100

H

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 10 of 20

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

Who

nee

ds p

harm

acol

ogic

th

erap

y?- P

atie

nts w

ith h

igh

(10-

year

pro

babi

lity

for m

ajor

oste

opor

otic

frac

ture

is ≥

20%

or t

he 1

0-ye

ar p

roba

-bi

lity

of h

ip fr

actu

re is

≥ 3%

) or v

ery

high

(10-

year

pro

babi

lity

for m

ajor

oste

opor

osis

frac

ture

> 30

%,

hip

frac

ture

> 4.

5%) f

ract

ure

risk

as a

sses

sed

by F

RA

X- P

atie

nts w

ith T

-sco

re o

f − 2.

5 or

low

er in

the

spin

e, fe

mor

al n

eck

or to

tal h

ip- P

atie

nts w

ith T

-sco

re b

etw

een −

1.0

and −

2.5

if th

e FR

AX

® (a

fter a

djus

tmen

t or r

ecal

cula

ted

usin

g TB

S if

avai

labl

e) 1

0-ye

ar p

roba

bilit

y fo

r maj

or o

steop

orot

ic fr

actu

re is

≥ 20

% o

r tha

t of h

ip fr

actu

re

is ≥

3%, w

here

ver a

pplic

able

usi

ng th

e co

untry

-spe

cific

thre

shol

ds- P

atie

nts w

ith im

min

ent f

ract

ure

risk

(hist

ory

of lo

w tr

aum

a fr

actu

re w

ithin

the

past

12 m

onth

s) o

r su

stai

ning

mul

tiple

frac

ture

s- P

atie

nts w

ho su

stai

n fr

actu

res w

hilst

on

oste

opor

osis

pha

rmac

olog

ical

ther

apy

- All

patie

nt w

ho a

re o

n lo

ng-te

rm th

erap

y (>

3 m

onth

s), o

r sus

tain

ing

frac

ture

s, w

hilst

on

med

icat

ion

that

may

impa

ct n

egat

ivel

y on

the

bone

hea

lth su

ch a

s lon

g-te

rm g

luco

corti

coid

s, an

drog

en d

eple

tion

ther

apy,

hor

mon

e an

tago

nist

ther

apy

- Pat

ient

s with

oste

opae

nia

(T sc

ore

from

− 1

to −

2.5)

who

hav

e m

oder

ate

risk

of fr

actu

re F

RA

X fr

ac-

ture

risk

pro

babi

lity

1–3%

at t

he h

ip a

nd 1

0–20

% a

t spi

ne m

ay b

e go

od c

andi

date

s for

pro

phyl

actic

zo

ledr

onic

aci

d ev

ery

18 m

onth

s for

4 in

fusi

ons [

20]

1A

8.92

0.5

100

H

Wha

t med

icat

ion

shou

ld b

e us

ed to

trea

t OP?

Ant

i-res

orpt

ives

:- B

isph

osph

onat

es: a

lend

rona

te, r

ised

rona

te a

nd z

oled

rona

te a

re a

ppro

pria

te a

s ini

tial t

hera

py fo

r mos

t os

teop

orot

ic p

atie

nts w

ith h

igh

frac

ture

risk

(gra

de 1

)- D

enos

umab

: app

ropr

iate

as i

nitia

l the

rapy

(if t

here

is c

ontra

indi

catio

n to

or i

ntol

erab

ility

to o

ral

bisp

hosp

hona

tes)

for o

steop

orot

ic p

atie

nts w

ith h

igh

frac

ture

risk

(gra

de 1

)- H

RT/ra

loxi

fene

: may

be

appr

opria

te in

itial

ther

apy

in so

me

case

s who

are

into

lera

ble

or h

ave

con-

train

dica

tions

to b

isph

osph

onat

e th

erap

yA

nabo

lics:

- Aba

lopa

ratid

e, te

ripar

atid

e- R

omos

ozum

ab c

an b

e co

nsid

ered

for p

atie

nts w

ho d

id n

ot re

spon

d po

sitiv

ely

(incr

ease

in th

e B

MD

) or

sust

ain

a fr

actu

re w

hilst

on

bisp

hosp

hona

te th

erap

y; o

r as i

nitia

l the

rapy

for p

atie

nts a

t ver

y hi

gh

frac

ture

risk

1 1 2 1 2

A A B A B

8.8

0.18

100

H

Archives of Osteoporosis (2021) 16:176

1 3

Page 11 of 20 176

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

Oste

opor

osis

pha

rmac

olog

ical

m

anag

emen

t:- O

ral b

isph

osph

onat

es (a

lend

rona

te, r

ised

rona

te) a

re fi

rst-l

ine

treat

men

ts in

the

maj

ority

of o

steop

oro-

sis c

ases

. Iba

ndro

nate

is n

ot re

com

men

ded

to re

duce

non

-ver

tebr

al o

r hip

frac

ture

risk

(gra

de 1

)- P

atie

nts a

ged ≥

65 y

ears

with

oste

opae

nia

(T sc

ore

from

− 1

to −

2.5

at e

ither

the

tota

l hip

or t

he

fem

oral

nec

k on

eith

er si

de) w

ho h

ave

mod

erat

e ris

k of

frac

ture

(10-

year

frac

ture

pro

babi

lity

at th

e hi

p in

the

rang

e of

1–3

% a

nd 1

0–20

% a

t the

spin

e) c

an b

e el

igib

le to

rece

ive

prop

hyla

ctic

trea

tmen

t zo

ledr

onic

aci

d 5 

mg

IV e

very

18 

mon

ths f

or 4

dos

es (g

rade

2b)

- In

oste

opor

otic

wom

en w

ho a

re in

tole

rant

of o

ral b

isph

osph

onat

es o

r in

who

m th

ey a

re c

ontra

indi

-ca

ted;

intra

veno

us b

isph

osph

onat

es o

r den

osum

ab p

rovi

de th

e m

ost a

ppro

pria

te a

ltern

ativ

es a

s ini

tial

ther

apy

(with

ralo

xife

ne o

r hor

mon

e re

plac

emen

t the

rapy

as a

dditi

onal

opt

ions

); ho

wev

er, t

his s

houl

d be

dec

ided

and

pre

scrib

ed b

y os

teop

oros

is sp

ecia

list (

grad

e 2a

)- O

ral a

nd in

trave

nous

bis

phos

phon

ates

are

con

train

dica

ted

in p

atie

nts w

ith h

ypoc

alca

emia

, hyp

er-

sens

itivi

ty to

bis

phos

phon

ates

and

seve

re re

nal i

mpa

irmen

t (eG

FR ≤

35 m

L/m

in fo

r ale

ndro

nate

an

d zo

ledr

onic

aci

d an

d ≤ 30

 mL/

min

for o

ther

bis

phos

phon

ates

). Pr

egna

ncy

and

lact

atio

n ar

e al

so

cont

rain

dica

tions

. Ora

l bis

phos

phon

ates

are

con

train

dica

ted

in p

eopl

e w

ith a

bnor

mal

ities

of t

he

oeso

phag

us th

at d

elay

oes

opha

geal

em

ptyi

ng su

ch a

s stri

ctur

e or

ach

alas

ia, a

nd in

abili

ty to

stan

d or

si

t upr

ight

for a

t lea

st 30

–60 

min

. The

y sh

ould

be

used

with

cau

tion

in p

atie

nts w

ith o

ther

upp

er g

as-

troin

testi

nal d

isor

ders

. Pre

-exi

sting

hyp

ocal

caem

ia m

ust b

e in

vesti

gate

d an

d, w

here

due

to v

itam

in D

de

ficie

ncy,

trea

ted

with

vita

min

D b

efor

e tre

atm

ent i

s ini

tiate

d (g

rade

2a)

- IV

zol

edro

nate

shou

ld b

e pr

escr

ibed

and

adm

inist

ered

onl

y by

oste

opor

osis

spec

ialis

t whe

n us

ed fo

r os

teop

oros

is m

anag

emen

t (gr

ade

2b)

- Den

osum

ab is

con

train

dica

ted

in w

omen

with

hyp

ocal

caem

ia o

r with

hyp

erse

nsiti

vity

to a

ny o

f the

co

nstit

uent

s of t

he fo

rmul

atio

n. It

s use

is n

ot re

com

men

ded

in p

regn

ancy

or i

n th

e pa

edia

tric

popu

la-

tion

(age

≤ 18

 yea

rs) (

grad

e 2a

)- M

onito

ring

of c

alci

um le

vels

shou

ld b

e co

nduc

ted

prio

r to

each

dos

e of

den

osum

ab a

nd w

ithin

2 

wee

ks a

fter t

he in

itial

dos

e in

pat

ient

s pre

disp

osed

to h

ypoc

alca

emia

(e.g

. pat

ient

s with

seve

re

rena

l im

pairm

ent,

crea

tinin

e cl

eara

nce ≤

30 m

L/m

in) o

r if s

uspe

cted

sym

ptom

s of h

ypoc

alca

emia

oc

cur o

r if o

ther

wis

e in

dica

ted.

Pat

ient

s sho

uld

be a

dvis

ed to

repo

rt sy

mpt

oms o

f hyp

ocal

caem

ia

(gra

de 2

a)- O

steop

orot

ic w

omen

age

< 60

 yea

rs o

ld a

nd le

ss th

an 1

0 ye

ars p

ast m

enop

ause

and

low

thro

mbo

sis

risk,

who

are

into

lera

nt to

bis

phos

phon

ates

and

den

osum

ab c

an b

e co

nsid

ered

for H

RT o

r SER

M:

* If

with

vas

omot

or sy

mpt

oms a

nd lo

w c

ance

r bre

ast r

isk,

HRT

can

be

used

* If

no

uter

us: o

estro

gen

* If

ute

rus i

s pre

sent

: oes

troge

n + pr

oges

tero

ne*

If w

ithou

t vas

omot

or sy

mpt

oms a

nd h

igh

canc

er b

reas

t ris

k, S

ERM

shou

ld b

e us

ed

1 2 2 2 2 2 2

A B A A B A A

7.33

183

.33

H

Cal

cium

and

vita

min

D d

aily

su

pple

men

tal t

hera

pyEv

ery

patie

nt sh

ould

be

taki

ng c

alci

um (1

 g/d

ay) a

nd v

itam

in D

(100

0 IU

/day

) sup

plem

ent t

hera

py in

ad

ditio

n to

the

oste

opor

osis

med

icat

ion.

The

dos

e ca

n be

adj

uste

d to

the

patie

nt-a

ssoc

iate

d co

mor

-bi

ditie

s- V

itam

in D

supp

lem

ent t

hera

py w

ith a

dai

ly d

ose

of 1

000

to 2

000

inte

rnat

iona

l uni

ts (I

U) i

s typ

ical

ly

requ

ired

to m

aint

ain

an o

ptim

al se

rum

25(

OH

)D le

vel.

How

ever

, hig

her d

oses

of v

itam

in D

3 m

ay b

e ne

cess

ary

in p

atie

nts w

ith p

rese

nt fa

ctor

s suc

h as

obe

sity

, mal

abso

rptio

n an

d ol

der a

ge- S

erum

25-

hydr

oxyv

itam

in D

(25[

OH

]D) s

houl

d be

mai

ntai

ned

in th

e ra

nge

of 3

0 to

50 

ng/m

L in

pa

tient

s with

oste

opor

osis

2A

8.92

0.5

100

H

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 12 of 20

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

How

is tr

eatm

ent m

onito

red?

- BM

D te

sting

can

be

used

to m

onito

r res

pons

e to

ther

apy

(gra

de 2

b)- F

RA

X c

an b

e us

ed to

mon

itor r

espo

nse

to th

erap

y (g

rade

5)

- Che

ck a

dher

ence

with

in 3

 mon

ths a

nd y

early

ther

eafte

r, in

clud

ing

tole

rabi

lity,

new

cau

tions

and

co

ntra

indi

catio

ns, c

alci

um/v

itam

in D

inta

ke, c

hang

e in

frac

ture

and

fall

risks

(gra

de 2

b)- M

onito

r BM

D se

rial c

hang

es in

lum

bar s

pine

, tot

al h

ip; i

f lum

bar s

pine

, hip

or b

oth

are

not e

valu

able

, m

onito

ring

with

1/3

radi

us si

te m

ay b

e ac

cept

able

but

is li

mite

d by

a sm

all a

rea

and

a ve

ry la

rge

leas

t si

gnifi

cant

cha

nge

(LSC

) (gr

ade

2b)

- Pat

ient

s mon

itorin

g, id

eally

, sho

uld

be c

arrie

d ou

t in

the

sam

e fa

cilit

y w

ith th

e sa

me

DX

A sc

anni

ng

syste

m, p

rovi

ded

that

the

acqu

isiti

on, a

naly

sis a

nd in

terp

reta

tion

adhe

re to

Inte

rnat

iona

l Soc

iety

for

Clin

ical

Den

sito

met

ry D

XA

bes

t pra

ctic

es (g

rade

3)

- In

the

case

of o

ral b

isph

osph

onat

e or

den

osum

ab, r

epea

t BM

D m

easu

rem

ent s

houl

d be

car

ried

out

afte

r ini

tial 2

 yea

rs o

f oste

opor

osis

ther

apy

to a

sses

s the

resp

onse

to tr

eatm

ent a

nd th

en a

t 5 y

ears

w

hen

the

patie

nt c

ompl

etes

the

treat

men

t cou

rse.

In th

e ca

se o

f IV

zol

edro

nate

, rep

eat D

XA

scan

sh

ould

be

carr

ied

out a

fter 3

 yea

rs o

f the

rapy

(gra

de 2

a)- A

t the

repe

at B

MD

ass

essm

ent c

arrie

d ou

t 2 y

ears

afte

r sta

rting

oste

opor

osis

ther

apy,

goo

d re

spon

se

to tr

eatm

ent i

s ide

ntifi

ed if

ther

e is

incr

ease

(inc

reas

e of

the

BM

D a

bove

the

prec

isio

n er

ror)

or

stab

ility

of B

MD

with

out t

he o

ccur

renc

e of

low

trau

ma

frac

ture

(gra

de 1

)- T

reat

men

t fai

lure

is c

onsi

dere

d w

hen

the

BM

D fa

lls si

gnifi

cant

ly fr

om b

asel

ine

(by

mor

e th

an th

e pr

ecis

ion

erro

r) o

r if f

urth

er fr

actu

res t

ook

plac

e de

spite

an

adeq

uate

tria

l and

adh

eren

ce to

dru

g tre

atm

ent

- How

ever

, it i

s im

porta

nt to

real

ise

that

eve

n th

e be

st tre

atm

ents

will

onl

y de

crea

se th

e fr

actu

re ra

te

(gra

de 2

a)- P

atie

nts s

houl

d co

ntin

ue to

rece

ive

the

sam

e tre

atm

ent f

or o

steop

oros

is d

urin

g th

e in

itial

2 y

ears

of

treat

men

t eve

n if

they

exp

erie

nce

a fr

agili

ty fr

actu

re (g

rade

2a)

- If a

pat

ient

rem

ains

at h

igh

frac

ture

risk

or d

evel

op a

frag

ility

frac

ture

, or m

ore,

afte

r 2 y

ears

of b

eing

on

the

sam

e tre

atm

ent,

in sp

ite o

f goo

d ad

here

nce

to th

erap

y an

d af

ter e

xclu

sion

of s

econ

dary

cau

ses,

then

con

side

r sw

itchi

ng to

ano

ther

ther

apy

(gra

de 2

a)- I

f a p

atie

nt h

as a

new

frac

ture

, dur

ing

thei

r tre

atm

ent b

reak

, the

y sh

ould

be

reas

sess

ed im

med

iate

ly

(gra

de 2

a)- D

urin

g tre

atm

ent,

all p

atie

nts s

houl

d be

enc

oura

ged

to m

aint

ain

good

ora

l hyg

iene

, rec

eive

rout

ine

dent

al c

heck

-ups

and

repo

rt an

y or

al sy

mpt

oms s

uch

as d

enta

l mob

ility

, pai

n or

swel

ling

(gra

de 2

b)- D

urin

g tre

atm

ent,

patie

nts s

houl

d be

adv

ised

to re

port

any

thig

h, h

ip o

r gro

in p

ain

and

any

patie

nt

pres

entin

g w

ith su

ch sy

mpt

oms s

houl

d be

eva

luat

ed fo

r an

atyp

ical

fem

ur fr

actu

re (g

rade

2b)

- Dur

ing

treat

men

t with

bis

phos

phon

ate

or d

enos

umab

, pat

ient

s sho

uld

be a

dvis

ed to

repo

rt ja

w p

ain,

sw

ellin

g or

gum

infe

ctio

ns; d

evel

opm

ent o

f exp

osed

bon

e in

the

mou

th a

long

eith

er th

e to

p or

bot

-to

m ja

ws;

loos

enin

g of

teet

h; p

oor h

ealin

g of

the

gum

s esp

ecia

lly a

fter d

enta

l wor

k or

num

bnes

s or a

fe

elin

g of

hea

vine

ss in

the

jaw

(gra

de 2

b)

2 3 2 1 2 2 2 2 2 2 2

B A A A A A B B B

8.9

0.1

86.7

6H

Trea

t-to-

targ

et: W

hat i

s suc

-ce

ssfu

l tre

atm

ent o

f oste

o-po

rosi

s?

- Tre

atm

ent t

arge

t: T

scor

e > −

1.5

– ‘lo

w fr

actu

re ri

sk’ (

from

clin

ical

and

/or s

cree

ning

tests

) sho

uld

be e

stab

lishe

d pa

rticu

larly

for p

ost-

frac

ture

pat

ient

s- F

ract

ure-

free

inte

rval

of 3

to 5

 yea

rs

2B

8.58

1.7

81.6

6H

Archives of Osteoporosis (2021) 16:176

1 3

Page 13 of 20 176

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

How

long

shou

ld p

atie

nts b

e tre

ated

?- O

ral b

isph

osph

onat

e tre

atm

ent s

houl

d la

st fo

r 5 y

ears

, whe

reas

for I

V z

oled

rona

te th

erap

y sh

ould

last

for 3

 yea

rs- C

ontin

uatio

n of

ora

l bis

phos

phon

ate

(ale

ndro

nate

and

rise

dron

ate)

trea

tmen

t bey

ond

5 ye

ars c

an

gene

rally

be

reco

mm

ende

d in

the

follo

win

g si

tuat

ions

:- F

ract

ure

risk

rem

ains

hig

h- T

-sco

re −

2.5

or le

ss- P

revi

ous h

istor

y of

a h

ip o

r ver

tebr

al fr

actu

re- C

urre

nt tr

eatm

ent w

ith o

ral g

luco

corti

coid

s ≥ 7.

5 m

g pr

edni

solo

ne/d

ay o

r equ

ival

ent

- Occ

urre

nce

of o

ne o

r mor

e lo

w tr

aum

a fr

actu

res w

hilst

on

ther

apy,

afte

r exc

lusi

on o

f poo

r adh

eren

ce

to tr

eatm

ent (

e.g.

less

than

80%

of t

reat

men

t has

bee

n ta

ken)

and

afte

r cau

ses o

f sec

onda

ry o

steop

o-ro

sis h

as b

een

excl

uded

. In

such

cas

es, c

lass

switc

hing

may

be

cons

ider

ed (g

rade

2a)

- Den

osum

ab th

erap

y sh

ould

initi

ally

last

for 5

 yea

rs (g

rade

2a)

. If d

enos

umab

ther

apy

is d

isco

ntin

ued,

pa

tient

s sho

uld

be tr

ansi

tione

d to

ano

ther

ant

ireso

rptiv

e- W

hene

ver i

ndic

ated

, the

follo

win

g th

erap

ies c

an b

eco

ntin

ued

for:

•10 

year

s—al

endr

onic

aci

d an

d de

nosu

mab

•7 y

ears

—ris

endr

onic

aci

d•3

 yea

rs—

zole

ndro

nic

acid

- Par

athy

roid

hor

mon

e th

erap

y 20

 μg

daily

for a

max

imum

dur

atio

n of

trea

tmen

t of 2

4 m

onth

s (gr

ade

2a).

The

med

icat

ion

shou

ld b

e fo

llow

ed b

y a

drug

inte

nded

for l

ong-

term

use

, suc

h as

a b

isph

osph

o-na

te o

r den

osum

ab) (

grad

e 1)

- Rom

osoz

umab

ther

apy

shou

ld la

st fo

r 12 

mon

ths.

The

med

icat

ion

shou

ld b

e fo

llow

ed b

y a

drug

in

tend

ed fo

r lon

g-te

rm u

se, s

uch

as a

bis

phos

phon

ate

or d

enos

umab

(gra

de 2

)

2a

8.58

0.82

91.7

6H

Dru

g ho

liday

- Dru

g ho

liday

can

be

cons

ider

ed a

fter c

ompl

etin

g 5 

year

s of o

ral b

isph

osph

onat

e/de

nosu

mab

ther

apy

or 3

 yea

rs o

f zol

edro

nate

IV th

erap

y if

the

targ

et o

f tre

atm

ent h

as b

een

achi

eved

(gra

de 2

a)- P

atie

nts w

ith lo

w to

mod

erat

e fr

actu

re ri

sk: c

onsi

der g

ivin

g bi

spho

spho

nate

then

stop

ping

for a

dru

g ho

liday

(gra

de 2

a)- O

nce

a ho

liday

has

beg

un, f

ract

ure

risk

and

BM

D sh

ould

be

re-e

valu

ated

eve

ry 1

to 3

 yea

rs a

fter

disc

ontin

uatio

n- T

he e

ndin

g of

a b

isph

osph

onat

e ho

liday

shou

ld b

e ta

ilore

d to

the

patie

nt’s

bon

e he

alth

stat

us, s

uch

as

a si

gnifi

cant

dro

p in

BM

D (b

y m

ore

than

a p

reci

sion

err

or) o

r inc

reas

e in

the

frac

ture

risk

may

lead

to

re-in

itiat

ion

of o

steop

oros

is th

erap

y, d

epen

ding

on

the

indi

vidu

al’s

frac

ture

risk

bef

ore

the

5-ye

ar

max

imum

hol

iday

is c

ompl

eted

- Pat

ient

s on

gluc

ocor

ticoi

ds (≥

7.5 

mg/

day)

or p

atie

nts w

ho h

ave

had

a ve

rtebr

al fr

actu

re sh

ould

not

us

ually

be

cons

ider

ed fo

r a tr

eatm

ent b

reak

2A

8.67

1.25

91.6

6H

Wha

t is t

he ro

le o

f con

com

itant

us

e of

ther

apeu

tic a

gent

s?C

ombi

natio

n th

erap

y of

par

athy

roid

hor

mon

e an

d de

nosu

mab

may

be

cons

ider

ed in

ver

y hi

gh fr

actu

re

risk

patie

nts.

This

shou

ld b

e co

nsid

ered

on

an in

divi

dual

bas

is; p

atie

nts s

houl

d be

ass

esse

d an

d m

an-

aged

by

oste

opor

osis

spec

ialis

t (gr

ade

2b)

2B

8.58

0.82

82.3

3H

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 14 of 20

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

Wha

t is t

he ro

le o

f seq

uent

ial

use

of th

erap

eutic

age

nts?

- In

postm

enop

ausa

l wom

en w

ith o

steop

oros

is a

t ver

y hi

gh ri

sk o

f fra

ctur

e, p

artic

ular

ly th

ose

with

his

-to

ry o

f oste

opor

otic

ver

tebr

al fr

actu

re, s

eque

ntia

l the

rapy

can

be

adop

ted

with

an

anab

olic

age

nt (e

.g.

abal

opar

atid

e, ro

mos

ozum

ab, t

erip

arat

ide)

follo

wed

with

a b

isph

osph

onat

e or

den

osum

ab to

pre

vent

bo

ne d

ensi

ty d

eclin

e an

d lo

ss o

f fra

ctur

e effi

cacy

- Seq

uent

ial t

hera

py st

artin

g w

ith p

arat

hyro

id h

orm

one

is a

n op

tion

for t

reat

men

t of o

steop

oros

is in

po

stmen

opau

sal w

omen

who

are

at v

ery

high

risk

for f

ract

ure

parti

cula

rly th

ose

who

hav

e pa

st hi

s-to

ry o

f mul

tiple

ver

tebr

al fr

actu

res.

This

shou

ld b

e de

cide

d an

d pr

escr

ibed

by

oste

opor

osis

spec

ialis

t- S

eque

ntia

l the

rapy

star

ting

with

rom

osoz

umab

is a

n op

tion

for t

reat

men

t of o

steop

oros

is in

pos

t-m

enop

ausa

l wom

en w

ho a

re a

t ver

y hi

gh ri

sk fo

r fra

ctur

e pa

rticu

larly

thos

e w

ho h

ave

past

histo

ry o

f hi

p or

ver

tebr

al fr

actu

res.

This

shou

ld b

e de

cide

d an

d pr

escr

ibed

by

oste

opor

osis

spec

ialis

t

2B

8.67

0.82

91.6

7H

The

role

of v

erte

bral

aug

-m

enta

tion

for c

ompr

essi

on

frac

ture

s?

Kyp

hopl

asty

/ver

tebr

opla

sty a

re n

ot re

com

men

ded

as fi

rst-l

ine

treat

men

t of v

erte

bral

frac

ture

s, gi

ven

an u

ncle

ar b

enefi

t on

over

all p

ain

and

a po

tent

ial i

ncre

ased

risk

of v

erte

bral

frac

ture

s in

adja

cent

ve

rtebr

ae (g

rade

1)

1A

8.67

0.5

84.1

H

Impl

emen

tatio

n of

FLS

Frac

ture

liai

son

serv

ices

(FLS

) sho

uld

be p

rovi

ded

for a

ll pa

tient

s sus

tain

ing

a fr

agili

ty fr

actu

re:

- Ens

ure

treat

men

t ini

tiatio

n w

ithin

8–1

2 w

eeks

of f

ract

ure

- FLS

shou

ld b

e pa

tient

-cen

tred

and

inte

grat

ed b

etw

een

orth

opae

dic

surg

ery,

orth

oger

iatri

cs, r

heum

a-to

logy

and

oste

opor

osis

cen

tres o

f car

e- P

hysi

cian

s sho

uld

follo

w u

p pa

tient

s at 4

and

12 

mon

ths t

o re

view

the

use

of m

edic

atio

ns th

at

incr

ease

the

risk

of fa

lls a

nd/o

r fra

ctur

e, to

ens

ure

co-p

resc

riptio

n of

cal

cium

and

vita

min

D w

ith

bone

pro

tect

ive

inte

rven

tions

and

to m

onito

r adh

eren

ce to

ther

apy

2A

8.83

0.5

100

H

The

impo

rtanc

e of

fall

asse

ss-

men

tFa

lls ri

sk sh

ould

be

asse

ssed

for e

very

pat

ient

eva

luat

ed fo

r fra

ctur

e ris

k (g

rade

2a)

2A

991

.4H

Oste

opor

osis

in m

enO

steop

oros

is sc

reen

ing

in m

en sh

ould

be

carr

ied

out i

n th

e ag

e of

70 

year

s or o

lder

- Men

at a

ge le

ss th

an 7

0 ye

ars o

ld c

an b

e as

sess

ed fo

r oste

opor

osis

if th

ey d

evel

op ri

sk fa

ctor

s- M

en w

ith o

steop

aeni

a (T

scor

e fro

m −

1 to

− 2.

5) w

ho h

ave

mod

erat

e ris

k of

frac

ture

FR

AX

frac

ture

ris

k pr

obab

ility

1–3

% a

t the

hip

and

10–

20%

at s

pine

may

be

good

can

dida

tes f

or p

roph

ylac

tic z

ole-

dron

ic a

cid

ever

y 18

 mon

ths f

or 4

infu

sion

s- F

or th

e pu

rpos

es o

f FR

AX

cal

cula

tions

, the

BM

D T

-sco

res i

n m

en a

re c

alcu

late

d ba

sed

on th

e fe

mal

e re

fere

nce

data

base

- Sec

onda

ry c

ause

s of o

steop

oros

is a

re c

omm

only

foun

d am

ongs

t men

, so

this

pop

ulat

ion

requ

ires

thor

ough

inve

stiga

tion

- Int

erve

ntio

n th

resh

olds

for m

en a

re si

mila

r to

thos

e re

com

men

ded

for w

omen

- All

men

star

ting

on a

ndro

gen

depr

ivat

ion

ther

apy

shou

ld h

ave

thei

r fra

ctur

e ris

k as

sess

ed- C

onsi

der r

efer

ring

men

with

oste

opor

osis

to sp

ecia

list c

entre

s, pa

rticu

larly

you

nger

men

or t

hose

w

ith se

vere

dis

ease

- Men

are

ass

esse

d an

d tre

ated

follo

win

g th

e sa

me

man

agem

ent p

roto

col s

ugge

sted

abov

e fo

r pos

t-m

enop

ausa

l wom

en, e

xclu

ding

the

HRT

2A

8.75

0.5

94.1

H

Archives of Osteoporosis (2021) 16:176

1 3

Page 15 of 20 176

Tabl

e 4

(con

tinue

d)

No

Dom

ain

Stat

emen

tsLE

GoR

Mea

n ra

teSD

% o

f ag

reem

ent

Leve

l of

agre

emen

t

Patie

nts o

n gl

ucoc

ortic

oids

th

erap

y- W

omen

and

men

age

≥ 70

 yea

rs, w

ith a

pre

viou

s fra

gilit

y fr

actu

re o

r tak

ing

high

dos

es o

f glu

coco

r-tic

oids

(≥ 7.

5 m

g/da

y pr

edni

solo

ne) s

houl

d be

con

side

red

for b

one

prot

ectiv

e th

erap

y, a

fter B

MD

ba

selin

e as

sess

men

t- I

n ot

her i

ndiv

idua

ls, f

ract

ure

prob

abili

ty sh

ould

be

estim

ated

usi

ng F

RA

X w

ith a

djus

tmen

t for

glu

co-

corti

coid

dos

e. B

asel

ine

BM

D a

sses

smen

t is a

dvis

ed- B

one-

prot

ectiv

e tre

atm

ent s

houl

d be

star

ted

at th

e on

set o

f glu

coco

rtico

id th

erap

y in

indi

vidu

als a

t m

oder

ate/

high

risk

of f

ract

ure

- Ale

ndro

nate

and

rise

dron

ate

are

first-

line

treat

men

t opt

ions

. Whe

re th

ese

are

cont

rain

dica

ted

or n

ot

tole

rate

d, z

oled

roni

c ac

id, t

erip

arat

ide

or d

enos

umab

(in

orde

r) a

re a

ltern

ativ

e op

tions

- Bon

e-pr

otec

tive

ther

apy

may

be

appr

opria

te in

som

e pr

emen

opau

sal w

omen

and

you

nger

men

, par

-tic

ular

ly in

indi

vidu

als w

ith a

pre

viou

s hist

ory

of fr

actu

re o

r rec

eivi

ng h

igh

dose

s of g

luco

corti

coid

s- F

or w

omen

in th

e ch

ildbe

arin

g pe

riod:

the

first-

line

ther

apy

is a

n or

al b

isph

osph

onat

e; se

cond

-line

th

erap

y is

a p

arat

hyro

id h

orm

one

2A

8.58

1.25

91.6

7H

COV

ID-1

9 an

d os

teop

oros

is- P

atie

nts d

o no

t war

rant

hig

her p

riorit

izat

ion

for v

acci

natio

n ag

ains

t CO

VID

-19

due

to th

eir o

steop

o-ro

sis

- Sta

ndar

d no

n-ph

arm

acol

ogic

app

roac

hes f

or o

ptim

izat

ion

of b

one

heal

th in

clud

e m

aint

enan

ce o

f vita

-m

in D

supp

lem

enta

tion,

mai

nten

ance

of a

dequ

ate

phys

ical

act

ivity

and

adh

eren

ce to

a b

alan

ced

diet

; th

ese

strat

egie

s sho

uld

be c

ontin

ued

beca

use

of th

eir m

uscu

losk

elet

al b

enefi

ts a

nd th

eir p

oten

tial

role

s as f

acili

tato

rs o

f im

mun

ocom

pete

nce

- Oste

opor

osis

ther

apie

s do

not i

ncre

ase

the

risk

or se

verit

y of

CO

VID

-19

infe

ctio

n an

d do

not

inte

r-fe

re w

ith th

e effi

cacy

or s

ide

effec

t pro

file

of C

OV

ID-1

9 va

ccin

es- O

ral b

isph

osph

onat

es, a

s wel

l as t

he se

lf-ad

min

ister

ed sk

elet

al a

nabo

lic a

gent

s, te

ripar

atid

e an

d ab

alop

arat

ide,

shou

ld n

ot b

e di

scon

tinue

d du

ring

vacc

inat

ion

It’s r

ecom

men

ded

an in

terv

al o

f 1 w

eek

betw

een

intra

veno

us b

isph

osph

onat

e in

fusi

on a

nd C

OV

ID-1

9 va

ccin

atio

n be

caus

e of

the

poss

ibili

ty o

f tre

ated

pat

ient

s dev

elop

ing

an a

cute

pha

se re

actio

n as

a

resu

lt of

adm

inist

ratio

n of

eith

er a

gent

- In

term

s of d

enos

umab

and

rom

osoz

umab

, it s

eem

s pru

dent

to a

llow

for a

n in

terv

al o

f 4 to

7 d

ays

betw

een

thes

e dr

ugs a

nd v

acci

natio

n be

caus

e of

put

ativ

e in

ject

ion

site

reac

tions

2B

8.63

0.82

94.1

H

LE, l

evel

of e

vide

nce

acco

rdin

g to

the

Oxf

ord

Cen

tre fo

r Evi

denc

e-B

ased

Med

icin

e (C

EBM

) crit

eria

; H, h

igh

leve

l of a

gree

men

t; GoR

, gra

de o

f rec

omm

enda

tions

; COVID

, cor

onav

irus d

isea

se

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 16 of 20

DXA machines. In other cases, it was linked to its prohibi-tive cost, even where the DXA machines are available [38]. Furthermore, the limitations of BMD for risk assessment have been one of the motives for the development of fracture risk prediction algorithms that integrate clinical risk factors for fracture. There are several fracture risk assessment tools available. Of these, the FRAX tool. (https:// www. sheffi eld. ac. uk/ FRAX/ tool. aspx) has been the most extensively used. FRAX calculates the 10-year probability of a major fracture

(clinical spine, humerus or wrist fracture) and 10-year prob-ability of a hip fracture. A unique feature of FRAX is that it is based on a countries’ epidemiological data and considers competing mortality in the fracture risk estimation proce-dure [19].

Unfortunately, in Africa, there is a huge treatment gap between those at risk of fracture and those receiving treat-ment for the prevention of fragility fractures. Both the eco-nomic and societal burden of osteoporotic fragility fractures

Fig. 2 An algorithm sum-marising the fracture-centric approach and the group’s consensus recommendations for the management of osteoporosis patients stratified according to their fracture risk. Case finding and management approach were set up according to the  fracture risk category.  The determina-tion of fracture risk was carried out based on fracture risk score calculation (e.g. FRAX) and the measurement of lumbar spine and hip BMD

Osteoporosis Screen Risk Factors

Low Moderate

BMD

High Very High

FRAX*Fracture Probability

Reassess Fracture Probability

HighNot High (Moderate)

*Calcium and Vitamin D suppl.*Risk appropriate exercise*Reassurance*Lifestyle advice

* Reassess when addi�onal risk factors develop

Bisphosphonates (oral/IV) for 3-5 years

Denosumab (5-10 years)

Or any other

an�resorp�ve +

Calcium and vitamin D suppl.

*AppropriateExercise*Lifestyle advice

Urgent referral to Osteoporosis specialist

Anabolic agent:

Romosozumab (1-year) or parathyroid hormone (18-24 months) therapy followed by inhibitor of bone resorp�on, then drug holiday#

*Consider cost effec�ve/biosimilar therapy

Consider Zoledronate (5mg IV) every 18-months, 4 doses-May consider oral bisphosphonate#Then stop for drug holiday.

Monitor Therapy: Clinic visit within 3-months then yearly. FRAX / BMD at 2 and 5-years from star�ng

Lifestyle modifica�ons: Recommended for all pa�ents irrespec�ve of risk Modifica�ons include: *exercise, strength, and balance training *diet *calcium/vitamin D *stop smoking *≤2 units/day alcohol *Tailor advice to each pa�ent’s own circumstances and comorbidi�es

Remain at high riskCon�nue Therapy or switch to another therapy, e.g. parathyroid hormone or romosozumab

Target: Treatment target: BMD: T score > − 1.5. Fracture risk below the treatment threshold or FRAX major osteoporosis fracture probability < 10%, hip fracture risk probability < 3%. Fracture-free interval of 3 to 5 years

Archives of Osteoporosis (2021) 16:176

1 3

Page 17 of 20 176

is enormous and is expected to rise owing to an increasing skew towards an older population [9, 10]. However, over the last two decades, there has been a significant shift towards the better ability to predict those at risk, using fracture pre-diction tools and an increasing understanding of scanning modalities, such as DXA or qualitative ultrasound scans [38]. This will allow appropriate earlier identification of patients with osteopenia or osteoporosis, who are at high or very high risk of fracturing, to benefit from osteoporo-sis therapy. Furthermore, a variety of generic therapeutic options are now available, at economically feasible prices. The developed guidelines endorse this armamentarium and provide a solid background to making appropriate treatment decisions, which is a step forward towards closing this gap in Africa.

The paradigm of treat-to-target aims at enhanced and individualised care of osteoporotic patients. Such strategy enables the treating clinicians to select the most appropriate initial osteoporosis therapy and guides subsequent decisions to continue, change or stop treatment [19, 33, 39]. Though some publications revealed that FRAX can be used to pre-dict new posttreatment fracture probability and assess the reduction in the fracture risk in women currently on osteopo-rosis therapy [40, 41], the predominant trend is that FRAX cannot be used to monitor response to therapy. On the other hand, repeat DXA informs on the long-term treatment effect on BMD. The new concept of very high fracture risk and the development of new intervention thresholds [30, 42] provide a new manifesto based on which this guideline has been developed. The very high fracture risk and the consequent further utility loss immediately after a subsequent fracture (imminent risk) suggest that preventive treatment given as soon as possible after fracture would avoid a higher number of new fractures and reduce the attendant morbidity, com-pared with the treatment given later [30, 43].

Monitoring of patients on osteoporosis therapy should include regular communication with a health care profes-sional to make sure that (1) the osteoporosis therapy is taken correctly and regularly as well as to ensure that treatment has been initiated within 16 weeks of non-traumatic frac-ture; (2) calcium and vitamin D supplement therapy are taken regularly and in appropriate dose (check adherence at 3 months and at 12 months); (3) address any concerns or adverse effects the patient might have; and (4) there are no comorbidities or other medications that might impact the expected treatment outcome. Whilst BMD is considered a surrogate marker for bone strength and fracture risk, stability or a significant increase in BMD is considered an acceptable treatment outcome and is associated with a reduction in frac-ture risk [44]. The time interval when treatment effect can be detected may vary depending on treatment modality, risk factors and current medications. A DXA scan should only be repeated if the results will impact the clinical management,

or if changes in BMD are expected to exceed the least sig-nificant change (LSC) for the DXA equipment used. The annual rates of loss during these intervals are approximately 1.8–2.3% in the spine and 1.0–1.4% in the hip. This is well below the least significant change (LSC), averaging 2–3% for most DXA machines at the total hip. Therefore, repeat DXA scan should be considered after 2–3 years of the for-mer scan, which has been recommended in this guideline. The target of bone mineral density (BMD) (in the range of − 1.5 to − 2) as suggested in this guideline agrees with those reported in other studies [19, 30, 39].

This guideline includes health care professionals from the entire African continent, ensuring that all the regions have been covered and represented; therefore, it is expected to be implemented across the whole of Africa. The aim is to streamline the osteoporosis service provided to the patients across the continent and ensure that osteoporosis therapy is determined or escalated according to the patient’s risk factors and fracture risk within an approved framework. The Delphi technique has proven to be a reliable measure-ment instrument in developing new concepts and setting the direction of future-orientated research [16]. In Delphi methodology, consensus usually arises when agreement or disagreement ranges from 50 to 80% [17]. In our work, the agreement ranged between 83.3 and 100%, indicating a strong trend amongst the African health care professionals to have a treat-to-target approach for osteoporosis manage-ment. These findings agree with the results of the Span-ish consensus on osteoporosis management [45] as well as the Egyptian guidelines for osteoporosis management [31], which revealed similar scores on the treat to target policy.

Limitations of the guideline This guideline reflects the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adher-ence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.

Plans for guideline revision This field of osteoporosis thera-peutics is in a rapid phase of development, and revision of the scope and content of the guideline will therefore occur on regular basis. Where necessary, the guideline will be updated.

In conclusion, with changing demography, the cost of treating osteoporosis is expected to increase considerably in Africa by the year 2030. Understanding of the impact of clinical risk factors can influence prevention and treatment of osteoporotic fractures. Therefore, it is vital to screen the

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 18 of 20

patients and stratify them according to their identified frac-ture risk. This was a wide and representative panel of experts who established consensus regarding the management of postmenopausal osteoporosis in Africa. It also expanded to give guidance for the management of osteoporosis in men and the potential role of fracture liaison service in standard practice. The algorithm developed in this study facilitates the incorporation of several recent developments into the standard patient management protocols.

Declarations

Conflicts of interest None.

References

1. International Osteoporosis Foundation (2018): what is osteopo-rosis? 2018. https:// www. iofbo nehea lth. org/ what- is- osteo poros is Accessed 31 July 2021

2. Johnell O, Kanis JA (2006) An estimate of the worldwide preva-lence and disability associated with osteoporotic fractures. Osteo-poros Int 17:1726–1733

3. Kanis J, Johnell O, Oden A, Sernbo I, Redlund-Johnell I, Dawson A, De Laet C, Jonsson B (2000) Long-term risk of osteoporotic fracture in Malmö. Osteoporos Int 11:669–674

4. Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427

5. Rashki Kemmak A, Rezapour A, Jahangiri R, Nikjoo S, Farabi H, Soleimanpour S (2020) Economic burden of osteoporosis in the world: a systematic review. Med J Islam Repub Iran 34:154

6. Handa R, Kalla AA, Maalouf G (2008) Osteoporosis in develop-ing countries. Best Pract Res Clin Rheumatol 22:693–708

7. Paruk F, Tsabasvi M, Kalla AA (2021) Osteoporosis in Africa—where are we now. Clin Rheumatol 40(9):3419–3428

8. Billek-Sawhney B (2019) Osteoporosis risk – think twice about bone density in Ethiopians African Americans. Int Phys Med Rehab J 4(3):91–94

9. Yumiko Kamiya, DESA, United Nations: department of eco-nomic and social affairs. Population Division United Nations Regional Workshop, Lilongwe, July 2016. https:// www. un. org/ devel opment/ desa/ pd/ sites/ www. un. org. devel opment. desa. pd/ files/ unpd_ ws201 607_ demog raphic_ trends_ in_ africa_ yk. pdf

10. Census Bureau Releases New Report on Aging in Africa, SEP-TEMBER 02, 2020. RELEASE NUMBER CB20-TPS.53. https:// www. census. gov/ newsr oom/ press- relea ses/ 2020/ aging- in- africa. html. Accessed 11 Aug 2021

11. National Institute of Aging. New census report on aging trends in Africa. https:// www. nia. nih. gov/ news/ new- census- report- aging- trends- africa. Accessed 2 Aug 2021

12. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65-94

13. Leclercq E, Leeflang MM, van Dalen EC, Kremer LC (2013) Vali-dation of search filters for identifying pediatric studies. J Pediatr 162:629–634

14. OCEBM Levels of Evidence Working Group (2011) The Oxford levels of evidence 2. Oxford Centre for Evidence-Based Medi-cine, Oxford

15. Von der Gracht H (2012) Consensus measurement in Delphi studies: review and implications for future quality assurance. Technol Forecast Soc 79(8):1525–1536

16. Rowe G, Wright G (1999) The Delphi technique as a forecasting tool: issues and analysis. Int J Forecast 15:353–375

17. Rayens MK, Hahn EJ (2000) Building consensus using the policy Delphi method. Policy Polit Nurs Pract 1(4):308–315

18. Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, Wales PW (2014) Defining consensus: a system-atic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol 67(4):401–409

19. Kanis JA, Johansson H, Oden A, McCloskey EV (2011) Guid-ance for the adjustment of FRAX according to the dose of glu-cocorticoids. Osteoporos Int 22:809–816

20. Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S, Wiessing KR, Bolland MJ, Bastin S, Gamble GD (2018) Frac-ture prevention with zoledronate in older women with osteope-nia. N Engl J Med 379(25):2407–2416

21. Kinsella K, Wan H. An aging world: 2008. U.S. Census Bureau. International Population Reports. 2009; 9(1): 9

22. Gheita T, Hammam N (2018) Epidemiology and awareness of osteoporosis: a viewpoint from the Middle East and North Africa. Int J Clin Rheumatol 13(3):134–147

23. Ouzzif Z, Oumghar K, Sbai K et al (2012) Relation of plasma total homocysteine, folate and vitamin B12 levels to bone mineral density in Moroccan healthy postmenopausal women. Rheumatol Int 32(1):123–8

24. El Maghraoui A, Sadni S, El Maataoui A, Majjad A, Rezqi A, Ouzzif Z, Mounach A (2015) Influence of obesity on vertebral fracture prevalence and vitamin D status in postmenopausal women. Nutr Metab (Lond) 14(12):44

25. Ben Aissa R, Laatar A, Kerkeni S et al (2006) Prévalence de Et, l’ostéoporose chez les femmes ménopausées des gouvernorats de l’Ariana 119, de la Manouba-Tunis. Tun. Méd. 84(Suppl 10)

26. Haouichat C, Hammoumraoui N, Lehtihet S et  al (2014) SAT0461 Prevalence of postmenopausal osteoporosis in Alge-rian women. Ann Rheum Dis 73:760

27. Paruk F, Matthews G, Cassim B (2017) Osteoporotic hip frac-tures in Black South Africans: a regional study. Arch Osteo-poros 12(1):107

28. Cauley JA, Wu L, Wampler NS et al (2007) Clinical risk factors for fractures in multi-ethnic women. the women’s health initia-tive. J Bone Miner Res 22:1816–1826

29. Peled R, Dahan D, Endevelt R et al (2007) Osteoporosis among Ethiopian immigrant women: a risk analysis. Arch Osteoporos 2:45–52

30. El Miedany Y, Abu-Zaid MH, El Gaafary M et al (2021) Egyp-tian consensus on treat-to-target approach for osteoporosis: a clinical practice guideline from the Egyptian Academy of bone health and metabolic bone diseases. Egypt Rheumatol Rehabil 48:5. https:// doi. org/ 10. 1186/ s43166- 020- 00056-9

31. Amod A, Ascott-Evans B, Brown S, Cassim B, Davey M, de Lange W, de Villiers T et  al (2017) South African clinical guideline for the diagnosis and management of osteoporosis: JEMDSA 2017; 22(1) (Supplement 1)

32. Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, Harris ST, Hurley DL, Kelly J, Lewiecki EM, Pes-sah-Pollack R, McClung M, Wimalawansa SJ, Watts NB (2020) American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update. Endocr Pract 26(Suppl 1):1–46

Archives of Osteoporosis (2021) 16:176

1 3

Page 19 of 20 176

33. Kanis J, Cooper C, Rizzoli R et al (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30:3–44

34. Meeta M, Harinarayan CV, Marwah R, Sahay R, Kalra S, Bab-hulkar S (2020) Clinical practice guidelines on postmenopausal osteoporosis: *an executive summary and recommendations - update 2019–2020. J Midlife Health 11(2):96–112

35. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Sho-back D (2019) Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 104(5):1595–1622

36. UK consensus guideline on the management of patients at low, high, and very high risk of osteoporotic fracture. Cyrus Cooper, Kassim Javaid, Mary Elliott, David Stephens, Nuttan Tanna. www. Guide lines. co. uk 2020 [https:// www. guide lines. co. uk/ muscu loske letal- and- joint s-/ osteo porot ic- fract ure- guide line/ 455546. artic le ] accessed on 15th July 2021

37. National Osteoporosis Foundation. Joint guidance on COVID-19 vaccination and osteoporosis management from the American Society for Bone and Mineral Research (ASBMR), American Association of Clinical Endocrinology (AACE), Endocrine Soci-ety, European Calcified Tissue Society (ECTS), the International Osteoporosis Foundation (IOF), and the National Osteoporosis Foundation (NOF). Published online March 9, 2021. Accessed July 15, 2021. https:// www. nof. org/ news/ state ment- joint- guida nce- on- covid- 19- vacci nation- and- osteo poros is- manag ement- from- the- asbmr- aace- endoc rine- socie ty- ects- iof- and- nof/

38. Atiase Y, Quarde A (2020) A call to action for osteoporosis research in sub-Saharan Africa. Ghana Med J 54(1):58–67

39. Lewiecki EM (2017) Osteoporosis: Treat-to-Target. Curr Osteo-poros Rep 15(2):103–109

40. Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2012) Does osteoporosis therapy invalidate FRAX for fracture prediction? J Bone Miner Res 27:1243–1251

41. El Miedany YE, Gaafary ME, Yassaki AE, Youssef S, Nasr A, Ahmed I (2014) Monitoring osteoporosis therapy: can FRAX help assessing success or failure in achieving treatment goals? World J Rheumatol 4(2):14–21

42. Kanis JA, Harvey NC, McCloskey E et al (2020) Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporos Int 31:1–12

43. Lewiecki EM (2010) Bone density testing to monitor osteoporosis therapy in clinical practice. Am Fam Physician 82(7):749–754

44. Lewiecki EM, Watts NB (2008) Assessing response to osteopo-rosis therapy. Osteoporos Int 19(10):1363–1368

45. Nogués X, Nolla JM, Casado E, Jódar E, Muñoz-Torres M, Que-sada-Gómez JM, Canals L, Balcells M, Lizán L (2018) Span-ish consensus on treat to target for osteoporosis. Osteoporos Int 29(2):489–499

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Archives of Osteoporosis (2021) 16:176

1 3

176 Page 20 of 20

Authors and Affiliations

Y El Miedany1,2  · Farhanah Paruk3  · Asgar Kalla4  · A. Adebajo5  · Maha El Gaafary6  · Abdellah El Maghraoui7  · Madeleine Ngandeu8  · Dzifa Dey9  · Naglaa Gadallah10 · Mohamed Elwy10 · Farzana Moosajee11  · Mohammed Hassan  Abu‑Zaid12  · Salwa Galal10  · Soussen Miladi13  · Waleed Hassan14  · Abubaker Fadlelmola15 · Sally Saber10

Farhanah Paruk paruk@ukzn.ac.za

Asgar Kalla kallaa@iafrica.com

A. Adebajo a.o.adebajo@sheffield.ac.uk

Maha El Gaafary maha_elgaafary@med.asu.edu.eg

Abdellah El Maghraoui a.elmaghraoui@um5.net.ma

Madeleine Ngandeu ngandeum@yahoo.fr

Dzifa Dey dzifakay@gmail.com

Naglaa Gadallah naglagadallah@gmail.com

Mohamed Elwy elwy.mohamed@yahoo.com

Farzana Moosajee farzana@sun.ac.za

Mohammed Hassan Abu-Zaid drmhassan113@yahoo.com

Salwa Galal dr_salwa07@yahoo.com

Soussen Miladi Saoussenmiladi@gmail.com

Waleed Hassan waleed22101979@yahoo.com

Abubaker Fadlelmola Abubakerfadlelmola@gmail.com

Sally Saber Sally_saber@med.asu.edu.eg

1 Canterbury Christ Church University, Canterbury, UK2 King’s College, London, UK3 University of KwaZulu-Natal, Durban, South Africa4 University of Cape Town, Cape Town, South Africa5 University of Sheffield, Sheffield, UK6 Community and Public Health, Ain Shams University, Cairo,

Egypt7 Mohamed V University, Rabat, Morocco8 Faculty of Medicine and Biomedical Sciences, The

University of Yaoundé 1, Yaoundé, Cameroon9 University of Ghana Medical School, Accra, Ghana10 Rheumatology and Rehabilitation, Ain Shams University,

Cairo, Egypt11 Tygerberg Hospital and Stellenbosch University, Cape Town,

South Africa12 Rheumatology and Rehabiliation, Tanta University, Tanta,

Egypt13 Faculty of Medicine of Tunis, University of Tunis El Manar,

Tunis, Tunisia14 Rheumatology and Rehabilitation, Benha University, Benha,

Egypt15 Ahmed Gasim Teaching Hospital, Khartoum North, Sudan