1Diagnosis (postmenopausal women, men ≥ 50)
| T-score | Category |
|---|---|
| ≥ −1.0 | Normal |
| −1.0 to −2.5 | Osteopenia (low bone mass) |
| ≤ −2.5 | Osteoporosis |
| ≤ −2.5 + fragility fx | Severe (established) |
Use lowest T at L1–L4 spine, femoral neck, total hip. Use 1/3 distal radius if hyperparathyroidism, body weight > table limit, or hip/spine uninterpretable.
Premenopausal women, men < 50, kids: use Z-score; ≤ −2.0 = "below expected for age" — diagnose OP only with fragility fx or secondary cause.
Clinical Dx without low T: any hip or vertebral fragility fx; OR other fragility fx + osteopenia; OR osteopenia + Fracture Risk Assessment Tool (FRAX) above threshold.
2FRAX & treatment thresholds (US)
FRAX = WHO 10-yr probability of major osteoporotic fracture (MOF; hip, clinical spine, humerus, distal forearm) and hip fx alone.
Treat if: T ≤ −2.5 · OR hip/vertebral fragility fx (any T) · OR osteopenia + FRAX MOF ≥ 20% or hip ≥ 3%.
FRAX inputs: age, sex, wt/ht, prior fx, parent hip fx, smoking, glucocorticoid (GC) use, RA, secondary OP, alcohol ≥ 3/d, ± femoral-neck bone mineral density (BMD).
FRAX caveats (under-estimates): high-dose GC (> 7.5 mg/d → ×1.15 MOF, ×1.2 hip), multiple/recent fx, type 2 diabetes mellitus (T2DM), low trabecular bone score (TBS), fall risk.
3Risk tiers (AACE 2020) — drives drug choice
| Tier | Defining | First-line |
|---|---|---|
| High | T ≤ −2.5, or osteopenia + FRAX threshold, or older fragility fx | Oral bisphosphonate (BP; alendronate, risedronate); zoledronic acid (ZA) or denosumab if oral CI |
| Very high | Recent fx (< 12 mo); fx on therapy; multiple fx; T ≤ −3.0; FRAX MOF > 30% / hip > 4.5%; high fall risk; fx on chronic GC | Anabolic first (teriparatide, abaloparatide, romosozumab) → followed by antiresorptive |
4Screening
- All women ≥ 65 (USPSTF B; BHOF, AACE)
- Postmenopausal women < 65 if elevated risk by tool
- Men ≥ 70 (BHOF; USPSTF I-statement)
- Anyone ≥ 50 with fragility fx
- Chronic GC ≥ 3 mo regardless of age
- Aromatase inhibitor (AI) use (breast ca), androgen-deprivation therapy (ADT; prostate ca)
Modality: central dual-energy X-ray absorptiometry (DXA; lumbar spine + hip). quantitative computed tomography (QCT) / peripheral DXA / US: screen only.
5Secondary-cause workup (do before treating)
Always: CBC, CMP (Ca, Cr, alk phos, albumin), 25-hydroxyvitamin D (25-OH-D), TSH, intact parathyroid hormone (PTH), 24-h urine Ca + Cr, serum protein electrophoresis (SPEP) + free light chains + urine protein electrophoresis (UPEP), tissue-transglutaminase IgA (tTG-IgA), total testosterone (men).
Selective: 24-h urine free cortisol or low-dose dex (Cushing); tryptase; iron studies; ACTH; prolactin; estradiol/FSH/LH.
Yield: ~30% women, 50–80% men have a secondary cause.
High-yield mimics: 1° hyperparathyroidism (cortical loss → low radius BMD), multiple myeloma (MM)/monoclonal gammopathy of undetermined significance (MGUS), hyperthyroidism, celiac, Cushing, hypogonadism (incl. AI/ADT), CKD–mineral bone disorder (CKD-MBD), anorexia nervosa, mastocytosis, RA, inflammatory bowel disease (IBD).
6Drug-by-scenario (memorize)
| Scenario | Pick |
|---|---|
| Standard postmenopausal OP, GI tolerant | Alendronate or risedronate PO |
| Adherence concern / oral GI intolerance | Zoledronic acid IV q1y |
| Recent hip fracture | ZA — mortality benefit (HORIZON-RFT) |
| Chronic kidney disease (CKD) estimated glomerular filtration rate (eGFR) < 35 | Denosumab (replete Ca/D) |
| AI-induced bone loss (breast ca) | Denosumab q6mo or ZA |
| ADT bone loss (prostate ca) | Denosumab 60 mg SC q6mo (HALT) |
| Younger postmenopausal + breast-ca risk | Raloxifene (also ↓ ER+ breast ca; no hip benefit; ↑ VTE) |
| Newly menopausal + vasomotor sx | Estrogen ± bazedoxifene |
| Very-high risk (recent/multiple fx, T ≤ −3.0) | Anabolic first: romosozumab (no recent CV), teriparatide, or abaloparatide → then antiresorptive |
| Glucocorticoid-induced osteoporosis (GIO) high/very-high risk | Oral BP, ZA, denosumab, or PTH analog; consider anabolic first in very-high |
| Premenopausal OP | Treat secondary cause; pharm only if fragility fx |
7Drug holidays — board favorite
| Risk after course | Oral BP | IV ZA |
|---|---|---|
| Low–moderate | Holiday at 5 yr; reassess q2–3y | Holiday at 3 yr |
| High / very high | Continue to 10 yr | Continue to 6 yr |
Denosumab: NO holiday. Stopping → rebound multiple vertebral fx within 6–18 mo. Transition to BP within ≤ 6 mo of last dose.
Anabolic must be followed by antiresorptive or BMD gains lost in < 12 mo.
8Adverse effects — buzzwords
- Osteonecrosis of the jaw (ONJ): rare at OP doses (~1/10k–100k pt-yr); ↑ with dental extraction, GC, chemo. Don't delay tx for cleanings; defer elective implants / major surgery.
- Atypical femoral fracture (AFF): subtrochanteric / diaphyseal, transverse; prodromal thigh/groin pain; ↑ Asian, ↑ > 5 yr BP. Image bilaterally if suspected.
- Oral BP: esophagitis — full water, upright 30–60 min, fasting; avoid if eGFR < 30–35.
- IV ZA: acute-phase rxn (~30%) first dose; AF signal (not replicated); avoid eGFR < 35.
- Denosumab: hypocalcemia (esp CKD); cellulitis; rebound vertebral fx on stop.
- Romosozumab: Boxed warning (BBW) ↑ MI, stroke, CV death (ARCH); contraindicated within 1 yr of MI/stroke.
- Teriparatide: prior osteosarcoma BBW removed 2020; still avoid prior radiation, Paget, ↑ alk phos.
- Raloxifene: ↑ venous thromboembolism (VTE); worsens hot flashes.
9Special populations
GIO (ACR 2022): any adult on prednisone ≥ 2.5 mg/d for > 3 mo → assess. Treat moderate / high / very-high risk pharmacologically. Anabolic agents conditionally recommended initial therapy in high or very-high risk. Continue therapy as long as GC continues.
Men: approved — alendronate, risedronate, ZA, denosumab, teriparatide, abaloparatide, romosozumab. Always check testosterone.
CKD: eGFR ≥ 35 → standard. eGFR 30–35 → avoid IV ZA. eGFR < 30 → exclude CKD-MBD; denosumab (watch hypoCa); teriparatide / abaloparatide if PTH not high.
Cancer-induced: AI in breast ca → denosumab or ZA. ADT prostate → denosumab q6mo (HALT: −62% vert fx).
Older adults: falls dominate; multifactorial fall prevention; parenteral therapy preferred when adherence poor.
10Calcium / vit D / lifestyle
- Calcium 1200 mg/d women ≥ 51 + men ≥ 71; 1000 mg/d men 50–70. Diet preferred (excess → kidney stones).
- Vitamin D 800–1000 IU/d; target 25-OH-D ≥ 30 ng/mL (AACE), ≥ 20 ng/mL (IOM).
- Weight-bearing + resistance + balance exercise.
- Smoking cessation; alcohol < 2/d (♀) / 3/d (♂); protein ≥ 1 g/kg/d.
- Fall prevention: review meds, vision, home, footwear.
11Monitoring
- DXA at 1–2 yr after start, then q2–3y if stable; same machine; change must exceed least significant change (LSC).
- C-terminal telopeptide (CTX) (resorption) / procollagen type 1 N-terminal propeptide (P1NP) (formation) at 3–6 mo for adherence/response; expect 30–50% suppression on antiresorptive, rise on anabolic.
- Treatment failure = ≥ 2 fragility fx on therapy or BMD ↓ > LSC despite adherence → re-eval secondary causes; switch (often to anabolic).
12Top board pearls
- ~⅔ of vertebral fx are clinically silent → vertebral fracture assessment (VFA) on DXA if height loss or chronic GC.
- Hip fx: 25–30% 1-yr mortality; about half never regain their prior level of function.
- 1° hyperparathyroidism preferentially affects cortical bone → check 1/3 distal radius.
- T2DM: BMD overestimates strength → use TBS / FRAX adjustment.
- Recent hip fx: give ZA — both fracture and mortality benefit (HORIZON-RFT, > 2 wks post-op).
- Don't stop denosumab cold — rebound vertebral fx within months.
- Anabolic first in very-high risk; reverse sequence (anabolic after BP/denosumab) blunts response.
- Romosozumab BBW = CV; alternative anabolic if recent MI/stroke.
- Premenopausal "OP" is almost always secondary — work up first.
- Asian ancestry + long-duration BP → AFF risk.
- Calcitonin and ibandronate: no hip-fx data — wrong answer for hip protection.
- Teriparatide / abaloparatide: up to 24 months — continue beyond only if high fracture risk persists.
13 · Abbreviations
- 25-OH-D
- 25-hydroxyvitamin D
- AACE
- Am. Assoc. Clinical Endocrinologists
- ACR
- Am. College of Rheumatology
- ACTH
- adrenocorticotropic hormone
- ADT
- androgen-deprivation therapy
- AF
- atrial fibrillation
- AFF
- atypical femoral fracture
- AI
- aromatase inhibitor
- alk phos
- alkaline phosphatase
- ASBMR
- Am. Soc. Bone & Mineral Research
- BBW
- boxed (black-box) warning
- BHOF
- Bone Health & Osteoporosis Foundation
- BMD
- bone mineral density
- BP
- bisphosphonate
- Ca
- calcium
- CBC
- complete blood count
- CI
- contraindication / contraindicated
- CKD
- chronic kidney disease
- CKD-MBD
- CKD–mineral bone disorder
- CMP
- comprehensive metabolic panel
- Cr
- creatinine
- CTX
- C-terminal telopeptide
- CV
- cardiovascular
- DXA
- dual-energy X-ray absorptiometry
- eGFR
- estimated glomerular filtration rate
- ER+
- estrogen-receptor positive
- FDA
- U.S. Food and Drug Administration
- FRAX
- Fracture Risk Assessment Tool (WHO)
- FSH
- follicle-stimulating hormone
- fx
- fracture
- GC
- glucocorticoid
- GI
- gastrointestinal
- GIO
- glucocorticoid-induced osteoporosis
- HRT
- hormone replacement therapy
- IBD
- inflammatory bowel disease
- IOM
- Institute of Medicine
- IU
- international units
- IV
- intravenous
- LH
- luteinizing hormone
- L1–L4
- lumbar vertebrae 1–4
- LSC
- least significant change
- MGUS
- monoclonal gammopathy of undetermined significance
- MI
- myocardial infarction
- MM
- multiple myeloma
- MOF
- major osteoporotic fracture
- NOF
- National Osteoporosis Foundation (now BHOF)
- ONJ
- osteonecrosis of the jaw
- OP
- osteoporosis
- P1NP
- procollagen type 1 N-terminal propeptide
- PO
- oral (per os)
- PTH
- parathyroid hormone
- QCT
- quantitative computed tomography
- RA
- rheumatoid arthritis
- SC
- subcutaneous
- SPEP
- serum protein electrophoresis
- T2DM
- type 2 diabetes mellitus
- TBS
- trabecular bone score
- tTG-IgA
- tissue-transglutaminase IgA
- TSH
- thyroid-stimulating hormone
- UPEP
- urine protein electrophoresis
- US
- ultrasound
- USPSTF
- U.S. Preventive Services Task Force
- VFA
- vertebral fracture assessment
- VTE
- venous thromboembolism
- WHO
- World Health Organization
- ZA
- zoledronic acid