What are the guidelines for managing osteoporosis?

Osteoporosis Management Guidelines

Risk Assessment and Diagnosis

Use FRAX as the primary tool for assessing fracture risk and setting age-dependent intervention thresholds in all patients with osteoporosis. 1, 2

• For men, use a female reference database for densitometric diagnosis of osteoporosis (T-score ≤ -2.5) 1, 2
• Consider trabecular bone score alongside BMD and FRAX to enhance fracture risk assessment 1, 2
• All patients with a prior fragility fracture should be considered for anti-osteoporosis treatment regardless of BMD 1, 2, 3
• Treatment thresholds: 10-year probability of ≥20% for major osteoporotic fractures or ≥3% for hip fractures based on US-adapted FRAX 1
• Risk factors include older age, female sex, prior fractures/falls, low body weight, parental hip fracture history, glucocorticoid use, smoking, excess alcohol, inflammatory conditions, and low BMD 3

Non-Pharmacological Interventions

All patients with osteoporosis should engage in combination exercise including balance training, flexibility exercises, endurance activities, and resistance/progressive strengthening exercises. 1, 2

• Ensure vitamin D (800-1,000 IU daily) and calcium (1,000-1,200 mg daily) repletion in all men above 65 years and postmenopausal women 1, 2
• Actively encourage smoking cessation and limiting alcohol consumption 1, 2
• Tailor exercise programs to individual patient needs and abilities; offer medical rehabilitation for patients with gait or balance impairments 1
• Recommend muscle resistance exercises (squats, push-ups) and balance exercises (heel raises, standing on one foot) 3

Pharmacological Management: First-Line Therapy

Oral bisphosphonates (alendronate or risedronate) are the first-line treatments for patients at high risk of fracture. 1, 2

Alendronate

• Dosing: 70 mg once weekly (therapeutically equivalent to 10 mg daily) 4, 5, 6
• Take with full glass of plain water (6-8 oz) first thing upon arising, at least 30 minutes before any food, beverage, or other medication 4
• Patient must remain upright (not lie down) for at least 30 minutes after administration 4
• Significantly improves BMD at lumbar spine (5.1-5.4%), total hip, and femoral neck 2, 6
• Once-weekly dosing enhances compliance and may reduce esophageal irritation compared to daily dosing 5, 6

Risedronate

• Effect is 10 times stronger than alendronate 7
• Reduces vertebral fracture risk by 62% radiographically and 69% clinically within the first year 7
• Reduces femoral neck fracture risk by 40% over 3 years, or 60% in patients with prevalent vertebral fractures 7
• Better gastrointestinal tolerability than alendronate (4.1% vs 13.2% endoscopically confirmed gastric ulcers) 7
• Improves BMD at lumbar spine, total hip, and femoral neck 2

Pharmacological Management: Second-Line Therapy

Denosumab or zoledronate are second-line treatments for patients at high risk of fracture who cannot tolerate or have contraindications to oral bisphosphonates. 1, 2

Denosumab

• Administered as 60 mg subcutaneous injection every 6 months 8
• Improves BMD at lumbar spine, femoral neck, and total hip 2
• Critical warning: Increased risk of multiple vertebral fractures after stopping, skipping, or delaying doses 8
• Do not stop treatment without discussing alternative therapy with physician 8
• Serious infections (skin, abdomen, bladder, ear, endocarditis) may occur more frequently 8
• Severe jaw bone problems (osteonecrosis) possible; dental examination recommended before starting 8
• Unusual thigh bone fractures can occur 8

Zoledronate

• Significantly improves lumbar spine BMD, femoral neck BMD, and total hip BMD 2

Pharmacological Management: Very High-Risk Patients

For patients at very high risk of fracture (recent vertebral fractures, hip fracture with T-score ≤-2.5, multiple fractures), initiate sequential therapy starting with a bone-forming agent followed by an anti-resorptive agent. 1, 2, 3, 9

Teriparatide

• Administered as subcutaneous injection 10
• Significantly improves BMD at lumbar spine (7.2%) and femoral neck (3.7%) 2, 10
• Black box warning: Caused osteosarcoma in rats; use limited to patients who cannot use other treatments 10
• Treatment duration typically limited to 2 years due to limited long-term safety data 10
• May cause transient hypercalcemia; instruct patients to report persistent nausea, vomiting, constipation, lethargy, or muscle weakness 10
• Orthostatic hypotension possible; patients should be prepared to sit or lie down immediately after injection 10
• Must be followed by anti-resorptive therapy to maintain gains 3, 9

Abaloparatide

• Considered appropriate first-line treatment for patients at very high risk based on available BMD data 1, 2

Romosozumab

• Sclerostin inhibitor that can be considered for very high-risk individuals 3, 9

Special Populations

Cancer Patients

• Offer BMD testing every 2 years (or more frequently if medically necessary) for patients prescribed drugs causing bone loss 2
• For patients with nonmetastatic cancer and osteoporosis (T-score ≤-2.5) or FRAX-estimated risk ≥20% major fractures/≥3% hip fractures, offer bone-modifying agents (oral/IV bisphosphonates or subcutaneous denosumab) 1
• Avoid hormonal therapies (estrogens) in patients with hormone-responsive cancers 1
• High-risk populations include: premenopausal women on GnRH therapies, postmenopausal women on aromatase inhibitors, men on androgen deprivation therapy, bone marrow transplant recipients, and patients on chronic glucocorticoids (>3-6 months) 1

Men with Osteoporosis

• Assess serum total testosterone as part of pre-treatment evaluation 1, 2
• Consider appropriate hormone replacement therapy in men with low total or free serum testosterone 1, 2
• Testosterone replacement significantly increases lumbar spine trabecular and cortical volumetric BMD 2

Glucocorticoid-Induced Osteoporosis

• Prevention and treatment recommended for patients taking ≥7.5 mg prednisone equivalent for >3 months, regardless of age or gender 7
• Risedronate reduces vertebral fracture risk by 70% in first year in this high-risk population 7

Monitoring and Adherence

Use biochemical markers of bone turnover to assess adherence to anti-resorptive therapy, measured at baseline and 3 months. 1, 2

• Decreases in bone turnover markers occur within 1 month, reaching maximum at 3-6 months 7
• Poor adherence is significant: up to 64% of men are non-adherent to bisphosphonates by 12 months 2
• Patient education and counseling are essential for adherence 1
• Fracture liaison services increase medication initiation and adherence by 38% vs 17% without such services (risk difference 20%), potentially reducing subsequent fractures 3

Critical Safety Considerations

• Bisphosphonates: Take with plain water only (not orange juice or coffee which markedly reduce absorption); remain upright 30 minutes; do not take at bedtime 4
• Stop bisphosphonates and consult physician if esophageal symptoms develop (difficulty swallowing, retrosternal pain, new/worsening heartburn) 4
• Denosumab: Never stop abruptly without transitioning to alternative therapy due to rebound fracture risk 8
• Teriparatide: Contents must not be transferred to a syringe; discard pen after 28 days even if solution remains 10
• All bone-modifying agents: Dental examination before starting; practice good oral hygiene; report jaw pain 8