# Osteoporosis: Bone Density Loss — Diagnosis, Treatment & Fracture Prevention

Osteoporosis is a systemic skeletal disease characterized by decreased bone mass and disrupted microarchitecture, leading to increased bone fragility and fracture risk. According to WHO, one in three women and one in five men over 50 suffer from osteoporosis. Over 8.9 million osteoporotic fractures occur worldwide annually — one fracture every 3 seconds. Hip fracture is the most severe complication: 20% of patients die within a year, and 50% lose the ability to walk independently.

Bone is a living, constantly remodeling tissue. Two cell types determine bone balance: osteoblasts (build new bone) and osteoclasts (resorb old bone). In youth, formation exceeds resorption — peak bone mass is reached by age 25–30. After 35–40, resorption begins to predominate — annual loss of ~0.5–1%. In women during the first 5–10 years after menopause, loss accelerates to 2–5% per year due to estrogen deficiency (bone's main 'protector'). RANK/RANKL/OPG system: osteoblasts release RANKL → activates osteoclasts. Osteoprotegerin (OPG) is a 'decoy' for RANKL, inhibiting resorption. Denosumab mimics OPG. Wnt signaling pathway: stimulates osteoblasts. Sclerostin (osteocyte product) blocks Wnt. Romosozumab is an anti-sclerostin antibody.

Non-modifiable: female sex, age >65, Caucasian/Asian ethnicity, family history of fractures (especially maternal hip fracture), early menopause (<45), low weight (<57 kg). Modifiable: smoking (reduces bone mass by 5–10%), alcohol (>3 units/day), calcium and vitamin D deficiency, physical inactivity, frequent falls. Secondary causes: glucocorticoids (>5 mg prednisolone >3 months — most common iatrogenic cause!), hypogonadism, hyperparathyroidism, hyperthyroidism, celiac disease, IBD, rheumatoid arthritis, type 1 diabetes, CKD, aromatase inhibitors, androgen deprivation therapy, anticonvulsants, long-term PPIs.

DEXA (DXA) — dual-energy X-ray absorptiometry — the gold standard. Measures bone mineral density (BMD) at lumbar spine (L1–L4) and proximal femur. Results expressed as T-score — deviation from peak bone mass of young healthy adults: T-score ≥ −1.0 — normal. T-score −1.0 to −2.5 — osteopenia. T-score ≤ −2.5 — osteoporosis. T-score ≤ −2.5 + fracture — severe osteoporosis.

DEXA screening indications: all women ≥65, all men ≥70, postmenopausal women <65 with risk factors, men 50–69 with risk factors, anyone after low-energy fracture, patients on glucocorticoids ≥3 months.

FRAX (Fracture Risk Assessment Tool) — online calculator for 10-year fracture probability. Considers: age, sex, BMI, prior fracture, parental hip fracture, smoking, alcohol, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, femoral neck BMD. Treatment threshold (US NOF): 10-year hip fracture risk ≥3% or major osteoporotic fracture risk ≥20%.

Laboratory tests: calcium, phosphorus, alkaline phosphatase, 25(OH)D (vitamin D), PTH, TSH, testosterone (in men), bone turnover markers (CTx — resorption, P1NP — formation), CBC, creatinine, protein electrophoresis (myeloma exclusion).

Vertebral fracture assessment (VFA): detects vertebral compression fractures, often asymptomatic (2/3 of vertebral fractures are clinically 'silent'). Indicated with height loss >4 cm or chronic back pain.

Calcium (Calcium): daily requirement 1000–1200 mg (preferably from food). Dairy (1 glass milk = ~300 mg), cheese, yogurt, sardines, broccoli, fortified foods. If dietary intake <800 mg — supplements: calcium carbonate (with meals, 40% elemental Ca) or calcium citrate (fasting, better absorbed with low acidity, 21% elemental Ca). Don't exceed 500–600 mg per dose — absorption drops.

Vitamin D (Cholecalciferol): target 25(OH)D level 30–50 ng/mL (75–125 nmol/L). Preventive dose: 800–2000 IU/d. Therapeutic (deficiency <20 ng/mL): 5000–7000 IU/d for 8–12 weeks, then maintenance. Important: vitamin D without adequate calcium is ineffective, and vice versa.

Physical activity: weight-bearing exercises stimulate osteoblasts through mechanical loading. Walking >30 min/day, balance exercises (tai chi reduces fall risk by 47%), stair climbing. Swimming and cycling are less effective for bones (no axial loading) but beneficial for muscles. Fall prevention: remove rugs, good lighting, grab bars, vision correction, reduce/eliminate sedatives.

Alendronate (Fosamax®) 70 mg once weekly and Risedronate (Actonel®) 35 mg once weekly — oral first-line bisphosphonates. Ibandronate (Boniva®) 150 mg once monthly — alternative, but weaker evidence for hip fracture. Zoledronic acid (Reclast®) 5 mg IV once yearly — most potent bisphosphonate, convenient when oral forms not tolerated.

Mechanism: incorporate into bone matrix → taken up by osteoclasts → inhibit farnesyl pyrophosphate synthase → osteoclast apoptosis. Efficacy: vertebral fracture reduction 40–70%, hip fracture reduction 40–50% (alendronate, zoledronic acid). Oral dosing rules: morning on empty stomach, swallow with full glass of water (>200 mL), remain upright 30–60 minutes, no food for 30 minutes (60 for ibandronate). Critical for bioavailability (<1%!) and esophagitis prevention.

Side effects: GI (esophagitis, nausea — oral), flu-like syndrome (IV zoledronic acid — 30% at first infusion), hypocalcemia (check Ca and vit D before starting), atypical femur fractures (with prolonged >5–7 year use — 3.2–100/100,000 patient-years), osteonecrosis of the jaw (rare — 1:10,000–1:100,000 in osteoporosis, higher with oncology doses). Dental examination before starting!

Denosumab (Prolia®) 60 mg SC every 6 months. Monoclonal antibody to RANKL — blocks the main osteoclast activation signal. Advantages: independent of GI function and kidneys (safe with eGFR <30), convenient schedule (2 injections/year), continuous BMD increase up to 10 years. FREEDOM + Extension: vertebral fracture reduction 68%, hip 40%. CRITICALLY IMPORTANT: cannot skip or discontinue without replacement! After denosumab cessation, 'rebound' occurs — sudden resorption surge, multiple vertebral fractures within 6–12 months. If discontinuing — mandatory transition to bisphosphonate (zoledronic acid 1–2 infusions).

Teriparatide (Forteo®) — recombinant parathyroid hormone fragment (PTH 1-34). 20 mcg SC daily. Mechanism: with intermittent administration (once daily) stimulates osteoblasts > osteoclasts → bone mass accrual. With constantly elevated PTH (hyperparathyroidism) — opposite effect. Efficacy: spine BMD increase 9–13% over 18 months. Vertebral fracture reduction 65%, non-vertebral 53%. Duration: maximum 24 months (afterward — mandatory transition to antiresorptive to preserve gained mass). Indications: severe osteoporosis, multiple fractures, bisphosphonate failure. Contraindications: Paget's disease, hypercalcemia, unexplained alkaline phosphatase elevation, prior skeletal radiation, open growth plates.

Romosozumab (Evenity®) 210 mg SC monthly × 12 months. Anti-sclerostin antibody — dual effect: stimulates formation + suppresses resorption. ARCH: 48% vertebral fracture reduction vs alendronate. Limitations: 12-month course only, then transition to antiresorptive. Increased cardiovascular risk — do not prescribe with MI/stroke in preceding 12 months.

Raloxifene (Evista®) — selective estrogen receptor modulator (SERM). 60 mg/d. Reduces vertebral fractures 30–50%, but not hip fractures. Additional benefit: 66% breast cancer risk reduction. Side effects: hot flashes, increased thrombosis risk (DVT/PE). Abaloparatide (PTHrP analog) — teriparatide alternative. HRT (hormone replacement therapy) — effective for postmenopausal osteoporosis but not first-line due to risks (breast cancer, thrombosis — WHI). Calcitonin — rarely used (minimal efficacy, increased cancer risk).

GCS are the most common cause of secondary osteoporosis. Prednisolone >5 mg/d >3 months → up to 12% BMD loss in the first year. Prevention is mandatory: calcium 1200 mg + vitamin D 800–2000 IU from GCS day one. With elevated FRAX risk or T-score <−1.5 — bisphosphonate (alendronate, zoledronic acid) or denosumab. In severe osteoporosis + GCS — teriparatide (superior to bisphosphonates in this setting, PATH study).

Bisphosphonates: reassess after 3–5 years. If low risk (T-score > −2.5, no fractures) — 'holiday' for 2–3 years (alendronate, risedronate) or 3–6 years (zoledronic acid, which persists in bone longer). If high risk — continue up to 10 years. Denosumab: holidays NOT possible (rebound). Continue or transition to bisphosphonate. Teriparatide/romosozumab: strictly limited course (24/12 months), then antiresorptive. Monitoring: DEXA every 2 years on therapy, bone turnover markers (CTx) for response assessment.

30% of all hip fractures occur in men. Mortality after hip fracture is higher in men than women (37% vs 20% at one year). Causes: hypogonadism (androgen deprivation for prostate cancer!), GCS, alcohol, smoking, vitamin D deficiency. Diagnosis and treatment are analogous — alendronate, zoledronic acid, denosumab are approved for men. Testosterone — only with confirmed hypogonadism, as supplement (not replacement) to specific therapy.

Height loss >2 cm/year or >4 cm from maximum; back pain after minimal trauma (compression fracture?); fracture from standing height fall; prolonged GCS use; early menopause; family history of hip fracture.

*This article is for informational purposes only and does not replace endocrinologist or rheumatologist consultation. Osteoporosis treatment should be conducted under medical supervision.*