Bone R2 2012 - medkorat.in.th · (Zollinger-Ellison syndrome) ... dominant hypocalcemia or sporadic...

BONE DISEASE FOR R2

By .. Rungnapa Laortanakul

Bone

Mineral Metabolism

•Hypercalcemia

•Hypocalcemia

•Vitamin D deficiency

Basic Bone Biology

•Osteoporosis

•Osteomalacia

Vitamin D synthesis and metabolism

Skin Major source

UVB

circulation

Previtamin D3 �

vitaminD3 via

thermal

isomerization

Parathyroid hormone

Vitamin D

PTH action

• Hypocalcimia �stimulate PTH secretion

• Bone� bone resorption � Ca,PO4

• Kidney � Ca resorption

PO4 excretion

Calcitriol

• Net effect is Ca PO4

Calcitriol

1,25-dihydroxyvitamin D

• Small intestine � resorption of Ca,PO4

• Bone � bone resorption

• Kidney � excretion of Ca,PO4

• Net effect is Ca PO4

• Clinical depend on time onset and level

• Normal level is 8.5-10.5 mg/dl

• Calcium level 10.5-12 mg/dl asymptomatic

• Calcium level >12 usually symptomatic

Hypercalcemia

Clinical presentation

• Renal

• Nephrolithiasis/ Nephrocalcinosis

• Nephrogenic DI

• Polydipsia/ Polyuria

• Distal RTA

• Renal insufficiency

• Chronic hypercalcemic nephropathy

�nephrocalcinosis

• GI

Constipation, Anorexia, Abdominal pain, Pancreatitis, Increase gastrin secretion � PU

• CNS

Anxiety, Depression, Cognitive dysfunction, Confuse, Psychosis, Coma

• CVS

Calcify valve, HT, Shortened QT interval

• Skeleton

Gout, Pseudogout, Chondrocalcinosis, Osteoporosis, Osteopenia, Osteitis fibrosa cystica

Causes of hypercalcemia

Parathyroid-dependent hypercalcemia

• 1°hyperparathyroidism

• 3°hyperparathyroidism

• Familial hypocalciuric hypercalcemia

• Lithium-associated

• Antagonist autoantibodies to the calcium-sensing receptor

Williams texbook 11th ed.

Parathyroid-independent hypercalcemia

• Neoplasm-PTHrP dependent

-Other humoral syndromes-Local osteolytic dz(including metastasis)

• PTHrP excess

(non-neoplasia)• Excess vit D action

-Ingestion of excess vit D or

vit D analogues-Topical vit D analogues-Granulomatous dz-Williams’ syndrome

• Thyrotoxicosis• Adrenal insufficiency

• Renal failure

-ARF

-CRF with aplastic bone dz

• Immobilization

• Jansen’s dz• Drugs :

vit A intoxication

milk-alkali syndromethiazide diuretics theophylline

Williams texbook 11th ed.

Hyper Ca

Clinical evaluation

Hx,PE,

e’lyte,BUN,Cr,PO4,ALP

S.PTH

PTH dependent PTH independent

Hemoconcentration orSerum protein abnormality

Ionized Ca

S&S malignancy

Search for occult malignancyChest radiographSerum/urine IEP

MammogramAbdominal/chest CT

Evaluate forOther causes of

PTH-independent

Select appropriate tx,

consider bisphosphonate

High

Normal

Normal

or highLow

PTH dependent

24-hr urine calcium & Cr

Uca < 100 mg/day

or Clca/Clcr < 0.01YES NO

PTH

normal

PTH

high 1°hyperparathyroidismLi

therapy

Stop Li

Ca

High

Ca

normal

Li induce hyperPTH

BMD

Review criteria

For surgery

Age<40

or Family hx

YES NO

Presumptive FHH;Consider family screening

Work up• Ca, PO4 level

• Film find evidence of bone abnormality

• Find the solid organ tumor eg. CXR

• Alkaline phosphatase � bone lysis

• Hyperchloric metabolic acidosis suggest hyperPTH

• TFT � hyperthyroidism

• Cortisol � adrenal insufficiency

• Intact PTH level �hyperparathyroidism

• PTH-rP, vit D

• Urine calcium

Primary hyperparathyroidism

Present in one of four ways:

1. Asymptomatic hypercalcemia detected by

routine biochemical screening

2. Symptomatic hypercalcemia

3. During evaluation for manifestations of

hyperparathyroidism such as osteopenia,

osteoporosis, or nephrolithiasis

4. Rarely, hyperparathyroid bone disease (osteitis

fibrosa cystica) or parathyroid crisis


• Adenoma

• Carcinoma

• Glandular hyperplasia

• MEN 1

• MEN 2A

• Familial hyperparathyroidism

Multiple endocrine neoplasiaType 1


(>90 percent)

Pituitary tumors (10 to 20 percent)

• Prolactinoma

• Growth hormone-secreting

• Corticotropin-secreting

• Non-hormone-secreting

Enteropancreatic tumors

(60 to 70 percent)

• Gastrinoma

(Zollinger-Ellison syndrome)

• Insulinoma

• Vasoactive-intestinal polypeptide-secreting

• Glucagonoma

• Pancreatic polypeptide-secreting

• Non-hormone-secreting

Other

Type 2A

• Medullary thyroid cancer

(>90 percent)

• Pheochromocytoma

(40 to 50 percent)

• Parathyroid hyperplasia

(10 to 20 percent)

• Cutaneous lichen amyloidosis

Type 2B


• Pheochromocytoma

• Other

-Mucosal neuromas

-Intestingal ganglioneuromas

-Marfanoid habitus

Familial medullary thyroid cancer (variant of 2A)


Band keratopathy

Subepithelial Ca-PO4 deposits in the cornea

Sub-periosteal resorption

Cystic brown tumorsChondrocalcinosis

National Institutes of Health Consensus Conference

in 2008

Asymptomatic PHPT candidates for surgery

• Age < 50 yr

• Serum calcium level ≥ 1.0 mg/dl (0.25 mmol/liter)

above upper limits of normal

• Cr.Cl reduced to 60 ml/min by MDRD equation no.7

• Osteoporosis by T-score

• History of kidney stones or fractures

J Clin Endocrinol Metab 94: 366–372, 2009

Symptomatic PHPT

Cohort studies : after parathyroidectomy

• BMD & fracture rate : improve

• Cognitive function : improve

• Kidney stones : incidence declines after surgery.

• CVD & premature death : decrease

Sestamibi scan

• Noninvasive

• Most popular

• Localize abnormal

parathyroid glands

• Quality varies

• Nonlocalizing sestamibi

-Multigland disease

-Small parathyroid gl.

-Coexistent thyroid dz.

Secondary and tertiary hyperparathyroidism2°hyperparathyroidism

•Severe chronic kidney disease

•Usually have low or normal serum calcium concentrations

•Prolonged disease, may develop hypercalcemia

'Adynamic bone disease‘

3°hyperparathyroidism

•Advanced renal failure

•Due to progression from appropriate parathyroid

hyperplasia to autonomous overproduction of PTH

UTD18.1

Milk-alkali syndrome

• Triad of hypercalcemia, metabolic alkalosis, and

renal insufficiency

• Associated with the ingestion of large amounts of

calcium and absorbable alkali

• Typically occurs in the setting of excess calcium

carbonate supplementation to treat osteoporosis

or dyspepsia

UTD18.1


• Metabolic alkalosis can directly stimulating calcium reabsorption in the distal tubule, thereby diminishing

calcium excretion

• Calcium-induced decline in renal function, due to renal

vasoconstriction

• Chronic hypercalcemia, renal structural injury, can also contribute to the inability to excrete the excess calcium

• Renal function usually returns to baseline after cessation of milk or calcium carbonate intake, but irreversible injury

can occur in patients who have prolonged hypercalcemia

UTD18.1


• What remains unexplained is the apparent

difference in sensitivity of individuals to increased

intake of calcium and alkali

• Some individuals may not suppress

calcitriol levels in response to large doses of

calcium carbonate

UTD18.1

Malignancies associated with hypercalcemia

Osteolytic metastases:

•Breast cancer

•Multiple myeloma

•Lymphoma

•Leukemia

Humoral hypercalcemia (PTHrP):

•Squamous cell carcinomas

•Renal carcinomas

•Bladder carcinoma

•Breast cancer

•Ovarian carcinoma

•Non-Hodgkin lymphoma

•CML

•Leukemia

•Lymphoma

1,25- dihydroxyvitamin D:

•Lymphoma (Non-Hodgkin, Hodgkin,

lymphomatosis/granulomatosis)

•Ovarian dysgerminomas

Ectopic PTH sectretion:

•Ovarian carcinoma

•Lung carcinomas

•Neuroectodermal tumor

•Thyroid papillary carcinoma

•Rhabdomyosarcoma

•Pancreatic cancer

UTD18.1

Treatment of hypercalcemia

• Saline therapy

• Loop diuretic

• Initiated routinely once fluid repletion had been

achieved to further increase urinary calcium

excretion

• Calcitonin

• Bisphosphonate

• Dialysis

UTD18.1

Calcitonin

• Reduce serum calcium by increasing renal calcium excretion

• Decreasing bone reabsorption via interference with osteoclast maturation

• Salmon calcitonin (4 international units/kg) is usually

administered IM or SC every 12 hour

• Limited to first 48 hours, even with repeated doses,

indicating the development of tachyphylaxis, perhaps due to receptor downregulation

UTD18.1

Bisphosphonates

• Intravenous zoledronic acid or pamidronate

Side effects

• Flu-like symptoms

(fever, arthralgias, myalgia, fatigue, bone pain)

• Ocular inflammation (uveitis)

• Hypocalcemia

• Hypophosphatemia

• Impaired renal function/nephrotic syndrome

• Osteonecrosis of the jaw

UTD18.1

Glucocorticoid

Responsible for the hypercalcemia associated …

•Excess ingestion of vitamin D

•Endogenous overproduction of calcitriol

(1,25-dihydroxyvitamin D)

• Chronic granulomatous diseases

eg, sarcoidosis

• Lymphoma

UTD18.1

Hypocalcemia

• Clinical manifestations of hypocalcemia depend

upon the severity and chronicity of hypocalcemia

• Each 1 g/dL reduction in the serum albumin

concentration will lower the total calcium

concentration by approximately 0.8 mg/dL

Clinical manifestations of hypocalcemiaAcuteNeuromuscular irritability (Tetany) •Paresthesias (peri-oral, extremities) •Muscle twitching •Carpopedal spasm •Trousseau's sign •Chvostek's sign •Seizures •Laryngospasm •Bronchospasm

Chronic•Ectopic calcification (basal ganglia) •Extrapyramidal signs •Parkinsonism •Dementia

Cardiac •Prolonged QT interval •Hypotension •Heart failure •Arrhythmia •Papilledema

• Subcapsular cataracts • Abnormal dentition • Dry skin

Major causes of hypocalcemia

Low PTH (hypoparathyroidism) Genetic disorders •Abnormal parathyroid gland development

•Abnormal PTH synthesis •Activating mutations of calcium sensing receptor (autosomal dominant hypocalcemia or sporadic isolated hypoparathyroidism) Post-surgical :

thyroidectomy, parathyroidectomy, radical neck dissection Autoimmune•Autoimmune polyglandular syndrome (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency)

•Isolated hypoparathyroidism due to activating antibodies to calcium sensing receptor Infiltration of the parathyroid gland :granulomatous, iron overload, metastases

Radiation induced destruction parathyroid glands Hungry bone syndrome (post parathyroidectomy) HIV infection

UTD18.1


Low PTH (hypoparathyroidism) Genetic disorders •Abnormal parathyroid gland development

•Abnormal PTH synthesis •Activating mutations of calcium sensing receptor (autosomal dominant hypocalcemia or sporadic isolated hypoparathyroidism)Post-surgical :

thyroidectomy, parathyroidectomy, radical neck dissection Autoimmune •Autoimmune polyglandular syndrome (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency)

•Isolated hypoparathyroidism due to activating antibodies to calcium sensing receptor Infiltration of the parathyroid gland :granulomatous, iron overload, metastases

Radiation induced destruction parathyroid glands Hungry bone syndrome (post parathyroidectomy) HIV infection


High PTH (secondary hyperparathyroidism in response to hypocalcemia) •Vitamin D deficiency or resistance •Parathyroid hormone resistance

• Pseudohypoparathyroidism • Hypomagnesemia

•Renal disease •Loss of calcium from the circulation

• Hyperphosphatemia • Tumor lysis • Acute pancreatitis • Osteoblastic metastases • Acute respiratory alkalosis • Sepsis or acute severe illness

Drugs

•Inhibitors of bone resorption (bisphosphonates, calcitonin), especially in vitamin D deficiency

•Cinacalcet

•Calcium chelators (EDTA, citrate, phosphate)

•Foscarnet (due to intravascular complexing with calcium)

•Phenytoin (due to conversion of vitamin D to inactive metabolites)

•Fluoride poisoning

Disorders of magnesium metabolism

•Hypomagnesemia can reduce PTH secretion or cause PTH resistance and is therefore associated with normal, low, or high PTH levels

UTD18.1

Approach to hypocalcemia

• Measure serum albumin

• Family history of hypocalcemia genetic cause

• Chronic hypocalcemia • Activating mutation of calcium sensing receptor

• Pseudohypoparathyroidism

• Acquired hypoparathyroidism • Postsurgical or autoimmune damage

• Autoimmune hypoparathyroidism • Isolated abnormality/polyglandular autoimmune syndrome type I

• Lab : iPTH, Cr, Mg, PO4, 25(OH) vitD

UTD18.1

N Engl J Med 2004;350:2068-79

PTH Correct

Ca

PO4 Mg 25(OH)D 1,25(OH)D Cr

Hypoparathyroid

Activating

mutation calcium

sensing receptor

Hypo Mg

PTH resistance

(pseudohypo-

parathyroid)

Vitamin D

deficiency

Chronic kidney

disease

UTD18.1

Osteoporosis

• Decrease bone strength and increase fracture

• Imbalance of bone resorption and bone formation

• Bone strength

• Structural properties : Size, Shape,

Microarchitecture

• Material properties : Mineral, Collagen

WHO definition of Osteoporosis

Diagnostic Category T-score

Normal > -1

Osteopenia -1 to -2.5

Osteoporosis ≤ -2.5

Severe Osteoporosis ≤ -2.5 and

≥ 1 fragility fracture

ข้อบ่งชี ในการส่งตรวจ BMD

Thai osteoporosis guideline

BMD (DEXA)

Central

•Lumbar spine (L1-L4)

•Femoral area

Peripheral

•Radius

Common causes for secondary osteoporosisEndocrine diseases GI disorders

• Diabetes mellitus

• GH deficiency (rare)

• Acromegaly (rare)

• Hypercortisolism

• Hyperparathyroidism

• Hyperthyroidism

• Premature menopause

• Male hypogonadism

• Gastrectomy

• Celiac disease

• Inflammatory bowel

disease

• Liver cirrhosis

• Chronic biliary tract obstruction

• Chronic therapy with proton pump inhibitors

European Journal of Endocrinology (2010) 162 1009–1020

Hematologic diseases Rheumatological

• Myeloma

• Monoclonal gammopathy of undetermined significance

• Lymphoma/leukemia

• Systemic mastocytosis (rare)

• Disseminated carcinoma

• Chemotherapy

• Rheumatoid arthritis

• Ankylosing spondylitis

• Systemic lupus

erythematosus


Other

Common causes for secondary osteoporosisCommon causes for secondary osteoporosis

• Osteogenesis imperfecta

• Anorexia nervosa

Glucocorticoid excess

• Glucocorticoids impairs skeletal health

• Inhibition of bone formation due to induction of

osteoblast and osteocyte apoptosis


Glucocorticoid excess

• Predominant spinal bone loss and vertebral

fractures

• Increased risk of falls due to muscular atrophy

and altered neuromuscular function

• Low doses of glucocorticoids (prednisolone 2.5–

7.5 mg/day) associated with a 2.6-fold higher risk

of vertebral fractures


Glucocorticoid-induce Osteoporosis

N Engl J Med 2011;365:62-70

Glucocorticoid-induce Osteoporosis

N Engl J Med 2011;365:62-70

• National osteoporosis foundation

• Prednisolone ≥ 5 mg/day for at least 3 months

• Yearly BMD testing

• Threshold for treatment : T-score ≤ 2.5

• Calcium 1200 mg/day, vitamin D 2000 units/day

• Bisphosphonate

• Teriparatide : only for patients at high risk

Hyperthyroidism

• Thyroid hormone excess

(suppressed TSH)

• Activation of thyroid

hormone receptor a on

osteoblasts and osteoclasts

results in enhanced bone

resorption and bone loss


Hyperthyroidism

Large study of 686 postmenopausal women

•serum TSH level < 0.1 mIU/l

•4x – 5x risk of hip and vertebral fractures

Meta-analysis of 21 studies indicated that

•thyroid hormone therapy for TSH suppression in

differentiated thyroid cancer

•subclinical hyperthyroidism is associated with

osteoporosis in postmenopausal women


Drug-induced osteoporosis

• Numerous drugs affect bone metabolism

interfere

• Absorption of vitamin D, Ca, and PO4

• Vitamin D metabolism and action

• Direct cellular effects on

osteoblasts, osteoclasts, and osteocytes

• Interference amount or quality of bone matrix

proteins



• TZDs (rosiglitazone and pioglitazone)

• Insulin sensitizers

• Act as agonists of the peroxisome proliferator-

activated receptor-gamma

• 3-5 fold higher risk of fractures of the humerus,

femur, and hip in postmenopausal women



• TZD

• Shunting pluripotent mesenchymal stem cells

Osteoblastic lineage Adipocyte




Drug class Examples Indications

Glucocorticoids Prednisolone Autoimmune diseases

Chemotherapeutic drugs Methotrexate, ifosfamide

Tyrosine kinase inhibitors Imatinib Chronic myelogenous

leukemia

Thiazolidinediones Rosiglitazone, pioglitazone Type 2 diabetes mellitus

Proton pump inhibitor Omeprazole and

pantoprazole

Peptic ulcer and reflux

diseases

Thyroid hormone L-thyroxine Replacement therapy for

hypothyroidism, thyroid

cancer

Anticonvulsants Valproic acid Chronic seizure disorders

Antidepressants Selective serotonin re-

uptake inhibitors

Chronic depression

Anti-retroviral drugs Tenofovir HIV disease

Diagnostic tests in the work-up of secondary osteoporosis


Diagnostic tests Purpose

CBC Anemia as in myeloma or celiac

disease, Leukocytosis as in leukemia

Renal and Liver function test Renal or liver failure, alcohol abuse

Ca and PO4 Primary hyperparathyroid, myeloma

Serum bone specific or ALP Paget’ disease, osteomalacia

Serum 25-hydroxyvitamin D Vitamin D deficiency, osteomalacia

Serum TSH Hyperthyroidism

FBS Diabetic mellitus

Intact PTH Primary hyperparathyroidism

Serum protein electrophoresis,

immunofixation

MGUS, myeloma


Diagnostic tests Purpose

Serum free testosterone Male hypogonadism

Serum CRP Chronic infection/inflammation

24 hour urine calcium excretion Hypercalciuria

Anti-tissue transglutaminase

antibodies

Celiac disease

Anti-HIV antibodies HIV disease, AIDS

Morning fasting serum cortisol after

dexamethasone suppression

Cushing’s syndrome

Serum tryptase levels, urinary

histamine excretion

Systemic mastocytosis

COL1A genetic testing Osteogenesis imperfecta

Iliac crest bone biopsy Systemic mastocytosis,

MGUS/myeloma,

osteomalacia, lymphoma/leukemia

Diagnostic tests in the work-up of secondary osteoporosis

Laboratory Evaluation

• CBC

• Renal function

• Chemistry : Ca, PO4, ALP, LFT

• ESR, CRP

• Thyroid function test

• 25- hydroxyvitamin D

• Gonadal function

Treatment of Osteoporosis

• Pharmacotherapy

• Secondary cause

• Lifestyle Modification

Factor Influencing Fractures

Hormone

Nutrition

Exercise &

Life style

Bone massBone

strength

Falls

Postural

reflexes

Soft tissue

padding

Fracture

Shape &

architecture

Material

properties

Lifestyle Modification

• Weight-bearing exercise : jogging, aerobic

dancing, jumping rope

• Physical activity : 30 min / most day of week

• Fall prevention

Treatment (NOF 2008)

• Postmenopausal women and men older than 50 yr

• A hip or vertebral fracture fracture

• T –score < -2.5 at femoral neck, total hip or spine

• Low bone mass (T –score -1 to -2.5 at femoral neck, total

hip or spine) with other prior fracture

• Low bone mass (T –score -1 to -2.5 at femoral neck, total

hip or spine) with secondary causes associated with high

risk fracture

• Low bone mass (T –score -1 to -2.5 at femoral neck, total hip or spine) and 10- yr probability of hip fracture ≥ 3% or

a 10-yr probability of any major osteoporosis related fracture ≥ 20%

การรักษาภาวะโรคกระดกูพรุน


Pharmacotherapy

Adequate Calcium and vitamin D intake

•NOF 2008 : -Ca 1200 mg per day,

-Vitamin D 800-1000 IU per day

•Thai :

-Ca ; 19-50 yr : 1000 mg per day, >50 yr : 800 mg per day

-Vitamin D : 400-800 IU per day

Which drugs should be used?

• Antiresorptive agents

• Bisphosphonate

• Calcitonin

• Hormone replacement therapy

• Selective estrogen receptor modulators

• Bone formative (anabolic) agents

• Teriparatide (1-34 PTH)

• Double action

• Strontium ranelate

• Targeting of bisphosphonates to bone, localized

release during osteoclastic bone resorption

• Intestinal absorption is low

• Taken with a glass of tap water and ≥ 30 min

before food or other fluids

• 40-60% absorbed bisphosphonate not bound to bone & not metabolized

• Eliminated unchanged by renal excretion

Bisphosphonate

Flu-like symptoms

• Bisphosphonates IV can block FPP production in

monocytes

• Accumulation of isopentenyl diphosphate (IPP)

• Because IPP is also a bacterial antigen,

peripheral blood T cells recognize this as

bacterial infection

• Releasing TNF-α and IFN-γ, increasing IL-6 and

CRP, and causing flu-like symptoms

• Associated with 1st bisphosphonate doses

Esophagitis and ulceration

• Before absorption, bisphosphonates taken orally

can bind to gastric cells

• Inhibition of FPP synthase rapidly leads to cell death.

• This may explain the ability of orally administered

N-BPs to cause esophagitis and ulceration

Osteonecrosis of the Jaw (ONJ)

• Rarely with oral bisphosphonates

• Most cases of Pt cancer with IV bisphosphonates

• Risk factors

-Cancer

-Concomitant therapies

(chemotherapy, radiotherapy and corticosteroids)

-Poor oral hygiene

-Comorbid eg. anemia, coagulopathy, infection

-Duration of exposure, and older age CKD

www.wondershare.com

Osteonecrosis

of Jaw

Prevention (recommend)

• Before use bisphosphonates :removal of all foci of

dental infection.

• Routine dental care

• Regular oral examinations

Osteomalacia

• Osteomalacia : disorder of mineralization of newly formed matrix in adults

• Rickets : disorder of defective mineralization of cartilage

in the epiphyseal growth plates of children, leading to widening of the ends of long bones, growth retardation,

and skeletal deformities.

Normal bone

Osteoporosis

Osteomalacia

Osteoporosis + osteomalacia

Suggest osteomalacia• Bone pain, tenderness

• Myopathy

• Pseudofracture• Increased alkaline P

Decreased bone mineralization and matrix

Decreased bone mineralization

with normal or increased matrix

Causes of osteomalaciaAbnormal vitamin D metabolism : 2° hyperparathyroidism & hypophosphatemia

Deficient intake or absorption•Dietary •Inadequate sunlight exposure •Malabsorption •Gastrectomy •Small bowel disease •Pancreatic insufficiency Defective 25-hydroxylation •Biliary cirrhosis •Alcoholic cirrhosis •Anticonvulsants Loss of vitamin D binding protein•Nephrotic syndrome Defective 1-alpha 25-hydroxylation •Hypoparathyroidism •Renal failure •Vitamin D-dependent rickets type 1 Defective target organ response to calcitriol •Vitamin D-dependent rickets, type II (Hereditary vitamin D resistant rickets, HVDRR)

Vitamin D

Causes of osteomalacia

Mineralization defects

Abnormal matrix

•Chronic renal failure

•Osteogenesis imperfecta

•Fibrogenesis imperfecta

•Axial osteomalacia

Enzyme deficiency

•Hypophosphatasia

Inhibitors of mineralization

•Fluoride

•Aluminium

•Bisphosphonates

Phosphate deficiency Decreased intake •Antacids Impaired renal reabsorption -Primary defects •X-linked hypophosphatemic rickets

(vitamin D resistant rickets, VDRR) •Hereditary hypophosphatemic rickets with hypercalciuria •Sporadic acquired hypophosphatemic rickets •Fanconi Syndrome-Wilson disease, cystinosis, multiple myeloma -Secondary defects •Primary hyperparathyroidism •Secondary hyperparathyroidism (renal tubular acidosis, type 1 and disorders of vitamin D metabolism) •Oncogenic osteomalacia

CLINICAL PRESENTATION

• Asymptomatic and present radiologically as osteopenia

• Proximal muscle weakness • Muscle wasting, hypotonia, and discomfort with movement

• Waddling gait

• Bone pain • lower spine, pelvis, lower extremities

• may be associated with tenderness to palpation

• dull & aching, aggravated by activity & weight bearing

• Fractures • may occur with little or no trauma

• ribs, vertebrae, long bones

• Skeletal deformities are infrequent in adults.

• Abnormal spinal curvature or deformity of the thorax or pelvis appears only in severe osteomalacia of long duration

• Looser zones : pseudofractures or narrow radiolucent lines

Two theories have been proposed:1. Stress fractures that have been repaired by the laying down of inadequately mineralized osteoid2. Result of erosion by arterial pulsations.

Disorder Phosphate Calcium ALP

Vit D deficiency with 2° hyper PTH

Low Low to low normal

Elevated

Metabolic acidosis Normal Normal Normal

Proximal RTA Low Normal Normal

Hypophosphatasia Normal Normal Low

Osteogenesis imperfecta and

axial osteomalacia

Normal Normal Normal

Osteoporosis Normal Normal Normal

Vitamin D deficiency

• 25-Hydroxyvitamin D levels are inversely associated with parathyroid hormone levels until the former reach 30 to 40

ng per milliliter, at which point PTH begin to level off (at

their nadir)

Vitamin D insufficiency ..

25-hydroxyvitamin D < 30 ng per milliliter

Vitamin D intoxication ..

25-hydroxyvitamin D > 150 ng per milliliter

Treatment

Preventive and Maintenance to Avoid Deficiency

•800–1000 IU of vitamin D3/day

•50,000 IU of vitamin D2 every 2 wk or every

month

Treatment of Deficiency

•50,000 IU of vitamin D2 every wk for 8 weeks

•Then repeat treatment for another 8 wk if 25-

hydroxyvitamin D <30 ng/ml

Bone R2 2012 - medkorat.in.th · (Zollinger-Ellison syndrome) ... dominant hypocalcemia or sporadic...

Documents

Transcript of Bone R2 2012 - medkorat.in.th · (Zollinger-Ellison syndrome) ... dominant hypocalcemia or sporadic...