What are the guidelines for managing osteoporosis?

Osteoporosis Management Guidelines

Risk Assessment and Diagnosis

FRAX is the appropriate tool for assessing fracture risk and setting intervention thresholds in osteoporosis, with thresholds being age-dependent 1, 2. This tool combines clinical risk factors with bone mineral density (BMD) measurements to estimate 10-year absolute fracture risk for hip, spine, shoulder, and forearm fractures 3.

• For men, use a female reference database for densitometric diagnosis of osteoporosis 1, 2. This represents a strong recommendation from the most recent guidelines.
• Trabecular bone score, when used with BMD and FRAX probability, provides additional useful information for fracture risk assessment 1, 2.
• All individuals with a prior fragility fracture should be considered for treatment with anti-osteoporosis medications 1, 2. This is a strong recommendation regardless of BMD measurements.
• Treatment thresholds include: T-score ≤-2.5 at femoral neck, total hip, or lumbar spine, OR 10-year probability ≥20% for major osteoporotic fractures, OR ≥3% for hip fractures based on FRAX 1, 2.

Non-Pharmacological Interventions

All patients with osteoporosis should engage in physical exercise and maintain a balanced diet 1, 2. This is a foundational recommendation across all guidelines.

• Ensure vitamin D and calcium repletion: 1,000-1,200 mg calcium daily and 800-1,000 IU vitamin D for adults over 65 years 1, 2.
• Exercise should include a combination of balance training, flexibility exercises, endurance exercise, and resistance/progressive strengthening exercises to reduce fracture risk from falls 1, 2.
• Actively encourage smoking cessation and limit alcohol consumption 1, 2. Both are established risk factors for osteoporosis.
• Weight-bearing and muscle resistance exercises (squats, push-ups) combined with balance exercises (heel raises, standing on one foot) should be pursued 3.

Pharmacological Management: First-Line Therapy

Oral bisphosphonates (alendronate or risedronate) are first-line treatments for individuals at high risk of fracture 1, 2. This represents the strongest recommendation from the most recent guidelines.

Alendronate

• Alendronate significantly improves BMD at the lumbar spine, total hip, and femoral neck 2.
• Must be taken with plain water first thing upon arising, at least 30 minutes before any food, beverage, or medication 4. Even orange juice or coffee markedly reduces absorption.
• Patients must remain upright for at least 30 minutes after administration to reduce esophageal irritation risk 4.
• Available as 70 mg once weekly, which provides continuous inhibition of bone resorption and represents a major advance in convenience 5.

Risedronate

• Risedronate improves BMD at the lumbar spine, total hip, and femoral neck 2.
• Reduces vertebral fracture risk by 62% radiographically and 69% clinically within the first year 6.
• Reduces femoral neck fracture risk by 40% over 3 years, or 60% in patients with prevalent vertebral fractures 6.
• Has significantly better gastrointestinal tolerability than alendronate (4.1% vs 13.2% endoscopically confirmed gastric ulcers) 6.

Pharmacological Management: Second-Line Therapy

Denosumab or zoledronate are second-line treatments for individuals at high risk of fracture 1, 2. These should be considered when oral bisphosphonates are contraindicated or not tolerated.

Denosumab

• Administered via 6-monthly subcutaneous injections, improving BMD at lumbar spine, femoral neck, and total hip 2.
• Warning: Increased risk of broken bones, including multiple spine fractures, after stopping, skipping, or delaying doses 7. Do not discontinue without discussing alternative therapy with your physician.
• Severe jaw bone problems (osteonecrosis) may occur 7. Dental examination should be performed before initiating therapy.
• May increase risk of serious infections, including endocarditis 7.

Zoledronate

• Significantly improves lumbar spine BMD, femoral neck BMD, and total hip BMD 2.
• Administered intravenously, offering an alternative for patients with gastrointestinal intolerance to oral bisphosphonates 2.

Pharmacological Management: Very High-Risk Patients

Sequential therapy starting with a bone-forming agent followed by an anti-resorptive agent should be considered for individuals at very high risk of fracture 1, 2. Very high-risk includes recent vertebral fractures, hip fracture with T-score ≤-2.5, or multiple fractures 3, 8.

Teriparatide

• Significantly improves BMD at the lumbar spine and femoral neck 2.
• In glucocorticoid-induced osteoporosis, increases lumbar spine BMD by 7.2%, total hip by 3.6%, and femoral neck by 3.7% 9.
• Warning: In rats, teriparatide caused osteosarcoma 9. While no increased risk has been observed in humans, this should be discussed with patients.
• Should not be used for more than 2 years due to limited long-term safety data 9.
• Must be followed by anti-resorptive therapy to maintain gains 1, 2.

Abaloparatide

• Considered an appropriate first-line treatment for patients with osteoporosis at very high risk of osteoporotic fracture 1, 2. This is based on available BMD data.

Romosozumab

• A sclerostin inhibitor that can be considered for very high-risk individuals 3, 10, 8.

Special Populations

Cancer Patients

• Patients with nonmetastatic cancer prescribed drugs causing bone loss should receive BMD testing every 2 years, or more frequently if medically necessary 1, 2.
• Specific high-risk populations include: premenopausal women receiving GnRH therapies, postmenopausal women receiving aromatase inhibitors, men receiving androgen deprivation therapy, patients with bone marrow transplantation history, and patients with chronic glucocorticoid use (>3-6 months) 1.
• Hormonal therapies for osteoporosis are generally avoided in patients with hormonal-responsive cancers 1, 2.
• For cancer patients meeting treatment thresholds, bone-modifying agents (oral bisphosphonates, IV bisphosphonates, or subcutaneous denosumab) may be offered 1.

Men with Osteoporosis

• Serum total testosterone should be assessed as part of pre-treatment evaluation 1, 2.
• Appropriate hormone replacement therapy should be considered in men with low total or free serum testosterone 1, 2.
• Testosterone replacement has shown significant increases in lumbar spine trabecular volumetric BMD and cortical volumetric BMD 2.

Glucocorticoid-Induced Osteoporosis

• Treatment is recommended for patients taking ≥7.5 mg prednisone daily (or equivalent) for >3 months, regardless of age or gender 6.
• Risedronate reduces vertebral fracture risk by 70% in the first year among patients on long-term glucocorticoid therapy 6.
• Fracture risk should be adjusted upward by 1.15 for major osteoporotic fractures and 1.2 for hip fractures if prednisone dose is >7.5 mg/day 11.

Monitoring and Adherence

Biochemical markers of bone turnover are appropriate tools to assess adherence to anti-resorptive therapy 1, 2. Measure at baseline and at 3 months to monitor adherence 11.

• Poor adherence is a significant issue: up to 64% of men are non-adherent to bisphosphonate therapy by 12 months 1, 11. This highlights the critical need for patient education and adherence monitoring.
• BMD testing should be repeated every 2 years to assess treatment response 2, 11.
• The use of fracture liaison services increases medication initiation and adherence by 38% compared with 17% for patients without these services 3. These comprehensive programs should be utilized when available.

Common Pitfalls and Caveats

• Before initiating bone-modifying agents, perform a dental screening exam to reduce the risk of medication-related osteonecrosis of the jaw 2. This is particularly important for denosumab and bisphosphonates.
• Never discontinue denosumab without transitioning to another anti-resorptive agent, as this dramatically increases the risk of multiple vertebral fractures 7.
• Bisphosphonates must be taken correctly (fasting, with water only, remaining upright) or absorption is markedly reduced and esophageal complications may occur 4.
• Treatment regimens should be adapted to individual baseline fracture risk rather than using a one-size-fits-all approach 1, 2.
• Anabolic agents must be followed by anti-resorptive therapy to maintain bone density gains 1, 2. Failure to do so results in rapid bone loss.