When should medication be started to treat low bone mass?

When to Start Medication Treatment for Low Bone Mass

Medication treatment for low bone mass should be initiated based on fracture risk assessment rather than bone mineral density (BMD) values alone, with bisphosphonates recommended for all postmenopausal women with T-scores ≤-2.5 and for those with T-scores between -1.0 and -2.4 who have elevated fracture risk based on FRAX assessment. 1

Diagnostic Criteria and Assessment

• Low bone mass (osteopenia) is defined as a BMD T-score between -1.0 and -2.4 standard deviations below the mean BMD value for a young woman at the femoral neck, lumbar spine, or both 1
• Osteoporosis is defined as a BMD T-score ≤-2.5 at the femoral neck, lumbar spine, or both 1
• DXA (dual-energy x-ray absorptiometry) is the standard method for measuring BMD and should be used for initial screening and follow-up to evaluate therapy 1
• Z-scores rather than T-scores should be used to define "low BMD" in premenopausal women 2

Treatment Initiation Algorithm

Definite Treatment Indications (Start Medication)

1. Osteoporosis (T-score ≤-2.5)

   • All postmenopausal women and men over age 50 with T-scores ≤-2.5 should receive pharmacologic treatment 1

2. History of Fragility Fracture

   • Individuals of any age with fragility fractures (especially hip, spine, wrist, or proximal humerus) should receive treatment regardless of BMD 1, 3
   • Individuals with one or more insufficiency fractures should receive treatment 1

3. High Fracture Risk Based on FRAX

   • Patients with osteopenia (T-scores between -1.0 and -2.4) who have a 10-year probability of hip fracture ≥3% or major osteoporotic fracture ≥20% based on FRAX should receive treatment 1

Individualized Treatment Considerations (Consider Medication)

1. Osteopenia with Risk Factors

   • For females over age 65 with low bone mass (T-scores between -1.0 and -2.4), an individualized approach is suggested regarding bisphosphonate treatment 1
   • Treatment decisions should consider additional risk factors such as:
     • Family history of hip fracture
     • Smoking
     • Glucocorticoid use >3 months
     • Rheumatoid arthritis
     • Alcohol use 1

2. Secondary Causes of Bone Loss

   • When secondary causes are identified (e.g., glucocorticoid therapy, cancer chemotherapy), treatment with bone-active agents should be considered even in premenopausal women 2

3. Progressive Bone Loss

   • Serial BMD testing showing statistically significant decrease in BMD may warrant therapy initiation in the setting of confirmed primary osteoporosis 1
   • Assessment of bone turnover markers can help identify those with ongoing bone loss who may need intervention 2

Monitoring and Follow-up

• BMD measurements should be repeated at approximately 2-year intervals after baseline 1
• Shorter intervals (1 to <2 years) are preferable after therapy has been initiated 1
• Patients at high risk for rapid bone loss (e.g., those on glucocorticoid therapy) require more frequent monitoring (1-year intervals) 1
• BMD measurements do not need to be repeated routinely in patients with osteopenia unless the baseline T-score is <-2.0 or risk factors develop 1
• Scan intervals <1 year are discouraged 1

Treatment Selection

• First-line therapy: Bisphosphonates are recommended as first-line treatment for both men and women with osteoporosis 1
• Second-line therapy: RANK ligand inhibitor (denosumab) is suggested for those with contraindications to or adverse effects from bisphosphonates 1
• For very high fracture risk: Sclerostin inhibitor (romosozumab) or recombinant PTH (teriparatide) followed by a bisphosphonate may be considered in females with very high fracture risk 1, 4

Common Pitfalls to Avoid

• Failure to evaluate for secondary causes of bone loss before initiating treatment, especially in premenopausal women 2
• Overlooking fracture risk assessment in patients with CKD, who have elevated fracture risk 5
• Undertreatment of men with osteoporosis, who often have greater morbidity and mortality from hip fractures than women 1
• Relying solely on BMD values without considering clinical risk factors for fracture 1
• Using T-scores instead of Z-scores when evaluating premenopausal women 2
• Scanning intervals that are too frequent (<1 year), which may not provide clinically meaningful information 1

Special Considerations

• For patients on treatment, BMD should be monitored to assess effectiveness, with the spine being optimal for monitoring treatment response 1, 6
• Patients should be scanned on the same DXA machine for accurate comparisons 1
• After cessation of pharmacologic therapy, serial BMD testing is encouraged to monitor for potential bone loss 1
• For denosumab, discontinuation can lead to increased multiple-fracture risk, requiring careful consideration before stopping therapy 6