Management of low bone density in young adults

Jennifer Walsh MBChB PhD FRCP FHEA

Senior Clinical LecturerMellanby Centre for Bone ResearchUniversity of Sheffield

Low bone density in young adults

• Who to measure

• Principles of management

• Specific situationso Idiopathic osteoporosiso Glucocorticoid induced osteoporosiso Premature ovarian failure

Who to measure?

• Hypogonadismo anorexia nervosa, athleteso early menopause, Depo-Provera, GnRH agonistso Turner, Kleinfelter’s

• Malabsorptiono coeliac disease, inflammatory bowel disease

• Inflammatory arthritis• Glucocorticoids• Low trauma fracture

FRAX not valid under 40 years

DXA: Z - score

> - 2.0 within the expected range for age

< - 2.0 below the expected range for age

ISCD 2007 position statement www.iscd.org

Principles of management

• Fracture risk is low in young people

• Identify and treat underlying causes

• Address modifiable risk factors

• Repeat BMD to identify low peak bone mass

• Reserve pharmacological treatment for high current risk of fracture

Fracture risk is low in young adults

Hui JCI 1988

Identify and treat underlying causes

• Common causes include:o Thyrotoxicosiso Coeliac diseaseo Vitamin D deficiencyo Prolactinoma / hypogonadism

• Consider o Osteogenesis imperfectao Cushing’s syndrome

Cohen J Women’s Health 2009

Address modifiable risk factors

• Calcium intake

Halioua Am J Clin Nutr 1989

50 g

400 mg

300 mg

300 mg

Recommended intake 800 to 1000 mg/day

Address modifiable risk factors

1.Kelley Int J Endo 2013 2. Nilsson Osteoporos Int 2013 3. Walsh JCEM 2008 4. Cundy BMJ 1994

• Weight-bearing exercise increases BMD in young women and men1,2

• Smoking cessation, alcohol moderation

• DMPA contraception3

o BMD increases on cessation4

Repeat BMD

• Low BMD may be due to genetically low peak bone masso Probably not associated with increased fracture risk until

menopausal

• Repeat BMD at 18-24 months can confirm stable BMD with low peak bone mass

Idiopathic osteoporosis

• Pre-menopausal women Z <-2.0 with no underlying causeo Poor bone microarchitecture and high marrow fato Reduced bone strength by FEA

Cohen JCEM 2011

Pharmacological treatment

Pharmacological treatment

• Consider treating if low BMD ando Ongoing bone losso Fractureo High dose steroids

• Most treatments not licensed for premenopausal womeno Make clear to patiento Involve patient in decision-making

• Raloxifene contraindicated in premenopausal women• Stop treatment when risk factors resolved

• Bisphosphonateso Case reports of neonatal hypocalcaemia and talipes equinovarus1,2,3

o Case series with normal pregnancy outcomes− N=21, 1 case Apert’s syndrome4

− N=24, high rate spontaneous miscarriage (21%)5

• Discuss family intentions / contraception

• Consider drugs with quicker offset?

Pharmacological treatment- pregnancy

1. Munns JBMR 2004 2. Dunlop Ann Rheum Dis 1990 3. Illidge Clin Oncol (R Coll Radiol) 19964. Levy Bone 2009 5. Ornoy Reprod Tox 2006

Idiopathic osteoporosis - teriparatide

Teriparatiden = 21 (4 non-responders)

Cohen JCEM 2013

Idiopathic osteoporosis - teriparatide• Persistence of effect?

BMD decreases after cessation1

• Fracture prevention?• Sequential therapy?

1. Cohen JCEM 2015

Glucocorticoid-induced osteoporosis

• Reserve treatment for bone loss, fractures or very high doses

Lekamwasam OI 2012

IOF guideline 2012

Premature ovarian failure

• Oestrogen replacemento Not if hormone-sensitive cancer, mantle radiotherapy

• Continue to age 50

• HRT vs COCP

• Transdermal vs oral

Anorexia nervosa

• Complex endocrinopathy and bone pathology• Best treatment is weight gain and return of menses

• Risedronate may increase BMD in adult women1

• Transdermal oestrogen best evidence in adolescents2

1. Miller JCEM 2011 2. Misra JBMR 2012

Summary

• Identify and treat underlying causes• Address modifiable risk factors

o Dairy intake and exercise• Reserve pharmacological treatment for high risk patients

o Very low BMD with fractures or bone losso Discuss off-license use with patiento Contraception

• Evidence base has improved in recent yearso Unlikely to ever have good fracture prevention data

Good reviews: Young adults Ferrari 2012 Osteoporos Int 23:2735–2748Anorexia Misra 2016 Int J Eating Disorders 49:3 276–292