Osteoporosis Evaluation
Patient & DEXA
Excluded from the definition: skull, face, fingers, toes.
FRAX isn't computed here — its coefficients are proprietary and country-specific. Run the official Sheffield FRAX tool (select United States — US has race-specific models) and type the results back in.
Enter DEXA T-scores or a fragility-fracture history
Provide at least one T-score (spine, hip, or femoral neck) or a fragility fracture to evaluate.
Medications
Search by drug, brand, class, mechanism, side effect, or contraindication.
Oral bisphosphonates
Oral bisphosphonate · alendronate, Fosamax, risedronate, Actonel
Dosing: Alendronate 70 mg PO weekly; risedronate 35 mg weekly or 150 mg monthly; ibandronate 150 mg monthly. Take on an empty stomach with 8 oz plain water, stay upright ≥30 min, nothing else by mouth for 30 min.
Mechanism: Bind hydroxyapatite and directly inhibit osteoclast-mediated resorption.
Fracture reduction: Vertebral 31–44%; Hip 26–40% (alendronate, risedronate); Nonvertebral 17–20%. Ibandronate has NOT been shown to reduce hip fracture.
Common: Dyspepsia / esophageal irritation (20–30%), myalgia (~4%).
Rare: Osteonecrosis of the jaw (<0.1%), atypical femoral fracture (0.02–0.1%).
Contraindications: CrCl <30–35 mL/min; hypocalcemia (correct first); esophageal abnormality (stricture, achalasia, varices); inability to remain upright 30 min.
Duration: Reassess at 5 years. If fracture risk no longer high (no recent fx, T-score > −2.5), consider a drug holiday with reassessment every 2–3 years; continue up to 10 years if risk remains high.
Source: NEJM 2023 (Walker & Shane); JAMA 2025 review; FDA labels
Zoledronic acid
IV bisphosphonate · zoledronic acid, zoledronate, Reclast, Aclasta
Dosing: 5 mg IV once every 12–18 months. Ensure vitamin D repletion and hydration before infusion.
Mechanism: Bind hydroxyapatite and directly inhibit osteoclast-mediated resorption (IV route bypasses GI limits of oral agents).
Fracture reduction: Vertebral 56%; Hip 42%; Nonvertebral 18%. Reduces vertebral fracture in men.
Common: Acute-phase reaction (fever, myalgia, headache) in ~30% after the first infusion; transient creatinine rise (~2%).
Rare: Osteonecrosis of the jaw (<0.1%), atypical femoral fracture (0.02–0.1%), hypocalcemia (<1%).
Contraindications: CrCl <35 mL/min; hypocalcemia (correct first).
Duration: Reassess at 3 years; up to 6 years in very-high-risk patients.
Source: NEJM 2023 (Walker & Shane); JAMA 2025 review; FDA label
Denosumab
RANKL inhibitor (monoclonal antibody) · denosumab, Prolia
Dosing: 60 mg subcutaneous every 6 months.
Mechanism: Monoclonal antibody against RANKL; blocks osteoclast formation, function, and survival. Not renally cleared.
Fracture reduction: Vertebral 68%; Hip 40%; Nonvertebral 20%.
Common: Eczema/dermatitis (3–10%), cellulitis (0.3–0.4%).
Rare: Osteonecrosis of the jaw (<0.1%), atypical femoral fracture (0.02–0.1%).
Contraindications: Hypocalcemia (correct before dosing — risk of severe hypocalcemia, especially in advanced CKD).
Do NOT delay >1 month or stop without a plan: discontinuation causes rebound bone loss and multiple vertebral fractures. Continue indefinitely OR bridge to a bisphosphonate before stopping.
Duration: Continuous — no drug holiday. Transition to a bisphosphonate if stopping.
Source: NEJM 2023 (Walker & Shane); JAMA 2025 review; FDA label
Raloxifene
Selective estrogen receptor modulator (SERM) · raloxifene, Evista
Dosing: 60 mg PO daily.
Mechanism: Estrogen-receptor agonist in bone, antagonist in breast/uterus.
Fracture reduction: Vertebral 40%; Hip — not demonstrated; Nonvertebral — not demonstrated (spine-only protection).
Common: Hot flashes (~10%), leg cramps (~7%), peripheral edema (~5%).
Rare: Venous thromboembolism (~0.9%); increased risk of fatal stroke.
Contraindications: History of VTE; stroke or established cardiovascular disease; pregnancy.
Boxed warning: increased risk of VTE and fatal stroke.
Duration: Continue while benefit outweighs VTE risk. Reduces invasive breast cancer risk — a reasonable choice in women at elevated breast-cancer risk with spine-predominant disease.
Source: NEJM 2023 (Walker & Shane); FDA label
Teriparatide / Abaloparatide
PTH / PTHrP receptor agonist · teriparatide, Forteo, abaloparatide, Tymlos
Dosing: Teriparatide 20 µg SC daily; abaloparatide 80 µg SC daily.
Mechanism: PTH-pathway agonists; intermittent dosing stimulates bone formation > resorption.
Fracture reduction: Teriparatide: Vertebral 74%, Nonvertebral 39%. Abaloparatide: Vertebral 87%, Nonvertebral 46%.
Common: Nausea (~20%), headache (~13%), hypercalcemia (3–6%), leg cramps (~3%), orthostasis after early doses.
Rare: Osteosarcoma — theoretical (seen in rats; not observed in human post-marketing cohorts).
Contraindications: Increased baseline osteosarcoma risk: Paget's disease, prior skeletal radiation, unexplained elevated alkaline phosphatase, open epiphyses, bone malignancy/metastases; hypercalcemia. Teriparatide CrCl <30 mL/min.
FDA removed the osteosarcoma boxed warning and the 2-year lifetime cap in Nov 2020. ~2 years remains typical practice; after stopping, MUST follow with an antiresorptive to preserve gains.
Duration: ~24 months typical, then transition to an antiresorptive (gains are lost without follow-on therapy).
Source: NEJM 2023 (Walker & Shane); FDA teriparatide label update Nov 2020; JAMA 2025 review
Romosozumab
Sclerostin inhibitor (monoclonal antibody) · romosozumab, Evenity
Dosing: 210 mg SC monthly for 12 months.
Mechanism: Anti-sclerostin antibody; dual action — increases bone formation AND decreases resorption.
Fracture reduction: Vertebral 73%; Hip 38%; Nonvertebral 19%.
Common: Arthralgia (8–13%), headache (5–7%), injection-site reactions (~5%).
Rare: Osteonecrosis of the jaw (rare), atypical femoral fracture (rare).
Contraindications: MI or stroke within the prior 12 months; hypocalcemia (correct first).
Boxed warning: increased risk of major adverse cardiovascular events (MI, stroke, CV death). Avoid in patients at high CV risk.
Duration: 12 months only, then MUST transition to an antiresorptive.
Source: NEJM 2023 (Walker & Shane); FDA label; JAMA 2025 review
Reference
Reading a DEXA — T-score vs Z-score, WHO categories
DXA (dual-energy X-ray absorptiometry) is the gold standard for BMD, measured at the lumbar spine (L1–L4) and proximal femur; the distal 1/3 radius is used when the spine/hip can't be assessed (bilateral hip replacements, severe degenerative disease).
T-score compares BMD to a healthy young-adult mean, in SD. Each 1 SD drop roughly doubles–triples fracture risk. Z-score compares to an age- and sex-matched mean; a Z ≤ −2.0 is "below the expected range for age" and should prompt a secondary-cause workup. Z-scores are preferred in premenopausal women, men under 50, and children.
| Category | T-score |
|---|---|
| Normal | ≥ −1.0 |
| Osteopenia (low bone mass) | −1.0 to −2.5 |
| Osteoporosis | ≤ −2.5 |
| Severe (established) | ≤ −2.5 + fragility fracture |
~70% of osteoporotic fractures occur in people who do not meet the −2.5 threshold — many happen in osteopenia or even normal BMD. DXA is falsely elevated by degenerative disc disease, aortic calcification, compression fractures, obesity, and T2DM; falsely low in very thin patients, post-laminectomy, or with height-losing vertebral fractures.
Fragility fracture — definition & why it's diagnostic
A fragility fracture results from force equivalent to a fall from standing height or less — one that wouldn't break healthy bone. Classic sites: spine, hip, wrist/forearm, humerus, pelvis (rib is common but not independently diagnostic). Skull, face, fingers, and toes are excluded.
A classic-site fragility fracture is diagnostic of osteoporosis even with a normal T-score (NEJM 2023; ACOG; NBHA expanded criteria). WHO "severe osteoporosis" = T ≤ −2.5 plus a fragility fracture.
A fragility fracture sharply raises imminent risk: ~7.6% re-fracture in the first year, ~11.6% within 2 years. Vertebral compression fractures are the most common and often asymptomatic — height loss >1.5 in (3.8 cm) should prompt vertebral fracture assessment.
The diabetes paradox — why DEXA misleads in T2DM
Type 2 diabetes raises measured BMD by 5–10% yet raises fracture risk 40–70% (hip ×1.79, vertebral +35%). Bone quality is impaired by AGE accumulation, cortical porosity, poor microarchitecture, low bone-formation markers, and microvascular disease.
Adjustments: DXA underestimates risk — consider reading each T-score 0.5 lower (−2.0 → −2.5). FRAX underestimates too — surrogate the "rheumatoid arthritis" input, subtract 0.5 from the femoral-neck T-score, or add 10 years to age; incorporate TBS if available.
Each 1% rise in HbA1c raises fracture risk ~8%; HbA1c >9% over 2 years → +29%. Hypoglycemia raises fall/fracture risk (RR 1.52). Diabetes duration >10 years further elevates risk.
Who to screen — USPSTF, BHOF, ACOG, AACE, Endocrine
Women
- USPSTF 2025: all women ≥65 (Grade B); postmenopausal women <65 at increased risk by a formal risk tool (Grade B).
- BHOF: all women ≥65; postmenopausal 50–64 with risk factors.
- ACOG: all ≥65; postmenopausal <65 at increased risk by a formal tool.
- AACE/ACE: all postmenopausal ≥65; 50–64 with risk factors or prior fracture.
- Endocrine Society: postmenopausal women at high fracture risk.
Men
- USPSTF 2025: insufficient evidence — I statement.
- BHOF: all men ≥70; 50–69 with risk factors.
- Endocrine Society: men >70; 50–69 with significant risk factors or fracture after 50.
1 in 5 men over 50 will have an osteoporotic fracture; fracture-related mortality is higher in men. Androgen-deprivation therapy for prostate cancer is a key male-specific risk factor. All osteoporosis drugs improve BMD in men; zoledronic acid reduces vertebral fracture in men.
Non-pharmacologic management
- Calcium 1000–1200 mg/day (diet + supplement if needed).
- Vitamin D 600–800 IU/day; many aim higher to reach 25(OH)D ≥30 ng/mL.
- Exercise — weight-bearing + muscle-strengthening; balance training for falls.
- Fall prevention — home safety, vision correction, deprescribe sedatives/orthostatic agents, PT.
- Lifestyle — stop smoking, limit alcohol to ≤3 drinks/day; address low BMI.
Monitoring & drug holidays
- Repeat DXA every 1–2 years initially, then every 2 years once stable.
- A decline >3–5% at the spine or >4–5% at the hip on therapy → check adherence, secondary causes, or change therapy. CTX/P1NP can gauge response.
- Bisphosphonate holiday: reassess after 5 yr oral / 3 yr IV. If risk no longer high (no recent fracture, T > −2.5), consider a holiday with reassessment every 2–3 yr; otherwise continue (up to 10 yr oral, 6 yr IV).
- No holiday for denosumab (rebound vertebral fractures) or after anabolics — always bridge to an antiresorptive.
Special populations
Glucocorticoid-induced: bone loss fastest in the first 3–6 months. Treat anyone on ≥2.5 mg prednisone/day for ≥3 months with added risk factors; bisphosphonates/denosumab first-line, teriparatide if very-high risk.
CKD: bisphosphonates contraindicated at CrCl <30–35; denosumab usable but watch for severe hypocalcemia; distinguish osteoporosis from renal osteodystrophy (PTH, Ca, phosphorus, vitamin D, alk phos).
Post-fracture: imminent risk is highest in the first 1–2 years. Fracture liaison services raise treatment initiation (38% vs 17%). Start therapy as soon as the fracture is stabilized.
Sources: USPSTF 2025 (JAMA), NEJM 2023 (Walker & Shane), JAMA 2025 review (Morin/Leslie/Schousboe), AACE/ACE 2020, Endocrine Society, BHOF, ACOG, NBHA. Educational reference — clinical decisions remain yours.