STEPTRACKERMUSCULOSKELETAL | PATHOLOGY + ENDOCRINE + PHARMACOLOGY | HIGH-YIELD REVIEW

Metabolic Bone Disease

Too little bone, poorly mineralized bone, or chaotic remodeling — told apart by four lab values.

FOCUS ON

Osteoporosis: ↓ bone mass, normal mineral and normal labs; postmenopausal estrogen loss → RANKL ↑; vertebral, hip, wrist fractures; DEXA T ≤ −2.5. Osteomalacia/rickets: ↓ mineralization (vitamin D or phosphate) → ↓ Ca²⁺/PO₄³⁻, ↑ PTH, ↑ ALP. Paget: isolated ↑↑ ALP, mosaic bone, big skull, deafness, osteosarcoma risk.

DISORDER

MECHANISM

FEATURES

CLUE · TREATMENT

Primary osteoporosis

Postmenopausal: ↓ estrogen → ↑ RANKL, IL-6 → ↑ osteoclast activity · senile: ↓ osteoblast function

Trabecular bone first: vertebral compression fractures (height loss, kyphosis), hip, distal radius

DEXA T-score ≤ −2.5 · labs normal

Secondary osteoporosis

Drugs and diseases that tip remodeling toward resorption

Glucocorticoids, hyperthyroidism, hyperparathyroidism, alcohol, smoking, heparin, PPIs, anticonvulsants, immobilization, anorexia, hypogonadism

Young patient with fractures → look for a cause

Osteoporosis — treatment

Slow resorption or build bone

Calcium, vitamin D, weight-bearing exercise; bisphosphonates; denosumab (anti-RANKL); teriparatide (intermittent PTH analog, anabolic); raloxifene; romosozumab (anti-sclerostin)

Bisphosphonates: pill esophagitis, jaw osteonecrosis, atypical femur fractures

Rickets

Children: unmineralized osteoid at growth plates (vitamin D deficiency, ↓ phosphate)

Bowed legs, rachitic rosary, craniotabes, widened wrists, Harrison groove, delayed fontanelle closure

Exclusively breastfed, dark skin, no sun

Osteomalacia

Adults: defective mineralization of new osteoid

Diffuse bone pain, proximal muscle weakness, Looser zones (pseudofractures)

↓ Ca²⁺, ↓ PO₄³⁻, ↑ PTH, ↑ ALP

Vitamin D deficiency — causes

Less made, absorbed or activated

Low sun, diet, fat malabsorption (celiac, CF, bariatric), liver disease (25-OH), CKD (1α-OH), anticonvulsants

Measure 25-OH vitamin D

X-linked hypophosphatemic rickets

PHEX mutation → ↑ FGF23 → renal phosphate wasting, ↓ calcitriol

Rickets with low phosphate, normal calcium; poor response to vitamin D alone

Phosphate + calcitriol; burosumab

Paget disease of bone

Localized disordered remodeling: lytic → mixed → sclerotic phases; SQSTM1

Older adults: bone pain, enlarging skull (hat size), hearing loss, bowed tibias, fractures; mosaic lamellar bone with cement lines

Isolated ↑↑ ALP · bisphosphonates

Paget — complications

Hypervascular, weak bone

High-output heart failure (AV shunts), osteosarcoma, nerve compression, osteoarthritis, fractures

New pain in a Paget bone → sarcoma

Scurvy

Vitamin C deficiency → defective collagen hydroxylation

Bleeding gums, perifollicular hemorrhages, corkscrew hairs, poor wound healing; children: subperiosteal hemorrhage, bone pain

Tea-and-toast diet, alcoholism

Mechanism — bone remodeling

OsteoblastsRANKL + M-CSF

→

RANK on precursors

→

Osteoclasts resorb

OPGDecoy receptor blocks RANKL

Estrogen ↑ OPG and ↓ RANKL — its loss after menopause tips the balance to resorption. Continuous PTH resorbs bone; intermittent PTH (teriparatide) builds it.

Lab comparison

DISEASE

Ca²⁺

PO₄³⁻

ALP

PTH

Osteoporosis

—

Osteopetrosis

—/↓

—

Paget

—

↑↑

—

Osteomalacia / rickets

↓

↑

Primary HPT

↑

↓

↑

Renal osteodystrophy

↓

↑

How it's tested

COMMON CONFUSIONOsteoporosis has too little normal bone; osteomalacia has plenty of matrix that isn't mineralized. Normal labs point to osteoporosis.

THE TRAPAn older man with only an elevated alkaline phosphatase, normal calcium and phosphate, and a growing hat size has Paget disease — not liver disease (check GGT).

YOUR APPROACHFracture pattern + age + drugs → Ca²⁺, PO₄³⁻, ALP, PTH, vitamin D → mechanism (resorption, mineralization, remodeling) → drug with its key side effect.

If you see… think…

Postmenopausal woman with height loss and vertebral fractures, normal labs → osteoporosis

Osteoporosis in a patient on long-term prednisone → glucocorticoid-induced

Bisphosphonate user with exposed jawbone after dental work → osteonecrosis of the jaw

Toddler with bowed legs and beaded ribs → rickets

Adult with bone pain, pseudofractures, ↓ PO₄³⁻, ↑ ALP → osteomalacia

Rickets unresponsive to vitamin D, low phosphate, ↑ FGF23 → X-linked hypophosphatemia

Older man with hearing loss, bigger hats, isolated ↑ ALP → Paget disease

Mosaic bone with irregular cement lines → Paget disease

Paget patient with new severe bone pain and mass → osteosarcoma

Anabolic osteoporosis drug given intermittently → teriparatide