What are the indications and contraindications for the various osteoporosis medications?

Osteoporosis Medication Indications and Contraindications

For postmenopausal women with osteoporosis (T-score ≤-2.5), start with oral bisphosphonates (alendronate 70mg weekly or risedronate 35mg weekly) as first-line therapy for 5 years, as they reduce hip, vertebral, and nonvertebral fractures with the best safety profile and lowest cost. 1

Primary Indications by Patient Category

Women with Established Osteoporosis (High Risk)

First-line options (all reduce hip and vertebral fractures):

• Alendronate, risedronate, zoledronic acid, or denosumab 1
• These four agents have "broad-spectrum" antifracture efficacy across spine, hip, and nonvertebral sites 2

Very high-risk patients (multiple vertebral fractures, hip fracture, very low T-scores, or advanced age with frailty):

• Start with anabolic agents: abaloparatide, romosozumab, or teriparatide 2
• These provide superior bone density gains and faster fracture risk reduction than antiresorptives 3, 4
• Must transition to bisphosphonate after completing anabolic therapy to prevent bone loss 2, 3

Men with Osteoporosis

• Bisphosphonates reduce vertebral fractures (weaker evidence than for women) 1
• Treatment approach mirrors women but with less robust data 1

Glucocorticoid-Induced Osteoporosis

Age ≥40 years, moderate-to-high fracture risk:

• Oral bisphosphonates over all alternatives 5, 6
• Hierarchy if oral bisphosphonates inappropriate: IV bisphosphonates → teriparatide → denosumab → raloxifene (postmenopausal women only) 5

Age <40 years, low risk:

• Calcium and vitamin D only (1,000-1,200mg calcium, 600-800 IU vitamin D) 5, 6

Age <40 years, moderate-to-high risk:

• Oral bisphosphonates preferred 6

Osteopenia (Low Bone Mass)

• Treat if 10-year major osteoporotic fracture risk ≥20% OR hip fracture risk ≥3% using FRAX 2, 7
• Decision based on individual risk-benefit discussion 1

Specific Medication Contraindications

Oral Bisphosphonates (Alendronate, Risedronate, Ibandronate)

Absolute contraindications:

• Esophageal abnormalities (achalasia, stricture, dysmotility) 2, 7
• Inability to stand/sit upright for 30-60 minutes 2, 7
• Active upper GI disease 8
• Hypocalcemia 7

Relative contraindications:

• GI malabsorption (gastric bypass, celiac disease, Crohn's disease) 2
• Creatinine clearance <35 mL/min (for zoledronic acid) 7

Denosumab

• No renal dose adjustment needed (advantage over bisphosphonates) 2
• Caution: Higher hypocalcemia risk with severe renal impairment 2
• Caution: Lack of safety data with immunosuppressive agents 5, 6
• Critical: Must transition to bisphosphonate when stopping to prevent rebound bone loss 2

Raloxifene

Contraindications:

• Active or history of venous thromboembolism 7
• Pregnancy or women of childbearing potential 7

Harms:

• Increased thromboembolic events, pulmonary embolism, stroke, cardiovascular death 1
• Hot flashes 1

Limited indication:

• Only for younger postmenopausal women at higher vertebral than hip fracture risk 9
• Postmenopausal women when other agents inappropriate 5, 6

Teriparatide/Abaloparatide (Anabolic Agents)

Contraindications:

• Paget's disease of bone 3
• Prior skeletal radiation 3
• Bone metastases or skeletal malignancies 3
• Hypercalcemia 1

Limitations:

• Maximum 2-year lifetime use 3, 10
• Daily subcutaneous injection burden 5, 6
• High cost 5, 2

Estrogen/Hormone Replacement Therapy

Strong recommendation AGAINST use for osteoporosis treatment 1

Harms:

• Increased stroke, venous thromboembolism, breast cancer, cardiovascular events 1, 10

Exception:

• May consider in younger postmenopausal women with menopausal symptoms AND low baseline risk for adverse events 11

Treatment Duration and Monitoring

• Bisphosphonates: 5 years oral, 3 years IV 2, 1
• Consider drug holiday after this period if not high-risk 2
• Do NOT monitor bone density during treatment (weak recommendation) 1
• Reassess fracture risk at end of treatment period 2

Common Pitfalls to Avoid

1. Using raloxifene or estrogen as first-line therapy - strong evidence against this due to cardiovascular/thrombotic risks 1

2. Starting antiresorptives before anabolics in very high-risk patients - prior bisphosphonate use attenuates anabolic benefits 3, 4

3. Stopping denosumab without transitioning to bisphosphonate - causes rapid bone loss and rebound fracture risk 2

4. Prescribing oral bisphosphonates to patients with esophageal disorders or inability to remain upright - increases serious GI complications 2, 7

5. Using IV bisphosphonates in patients with CrCl <35 mL/min - contraindicated due to renal toxicity 7

6. Treating low-risk patients <40 years with pharmacotherapy - calcium/vitamin D sufficient 5, 6