What treatment is recommended for an elderly woman with multiple fractures and previous anti-resorption therapy?

Treatment Recommendation for Elderly Woman with Multiple Fractures on Prior Anti-Resorptive Therapy

This patient requires immediate initiation of anabolic therapy with teriparatide or romosozumab, followed by mandatory sequential anti-resorptive treatment, as she represents a very high fracture risk case with treatment failure on prior anti-resorptive medications.

Risk Stratification

This patient meets criteria for very high fracture risk based on:

• Multiple fragility fractures (two pelvic fractures plus proximal humerus fracture) 1
• Treatment failure on prior anti-resorptive therapy 2, 3
• Elderly age with established osteoporosis 1

First-Line Treatment: Anabolic Therapy

Primary Recommendation: Teriparatide

Teriparatide (recombinant PTH 1-34) at 20 mcg subcutaneously once daily is the preferred initial treatment for this very high-risk patient who has failed anti-resorptive therapy 1, 4.

Rationale for anabolic therapy over continuing anti-resorptives:

• The American College of Rheumatology conditionally recommends PTH/PTHrP over anti-resorptives (bisphosphonates or denosumab) for patients at very high fracture risk 1
• Prior anti-resorptive therapy blunts the anabolic effect of bone-forming agents, but teriparatide remains effective even in this context 1
• Teriparatide reduces vertebral fractures by 65% and nonvertebral fractures by 53% in high-risk postmenopausal women 4, 5, 6
• The patient's multiple fractures while on anti-resorptive therapy indicate inadequate response, making continuation of the same therapeutic class inappropriate 2, 3

Treatment Duration and Monitoring

• Maximum treatment duration: 2 years (24 months) - teriparatide should not be used for more than 2 years during a patient's lifetime due to osteosarcoma risk observed in rat studies 4
• Administer with supplemental calcium (1000-1200 mg daily) and vitamin D (800 IU daily or sufficient to maintain 25(OH)D levels ≥30-50 ng/mL) 1, 4
• Check serum calcium at 1 month after initiation (>16 hours post-dose); mild hypercalcemia may occur but is typically transient 4, 3
• Initial administration should occur under circumstances where the patient can sit or lie down due to potential orthostatic hypotension 4

Alternative Anabolic Option: Romosozumab

Romosozumab (anti-sclerostin antibody) is an alternative anabolic agent with the following considerations:

• Limited to exactly 12 monthly subcutaneous doses as the anabolic effect wanes after this period 7
• May have superior anti-fracture efficacy compared to anti-resorptives in head-to-head studies 8
• Contraindicated if myocardial infarction or stroke within 12 months 1
• Requires careful cardiovascular risk assessment including evaluation for untreated hyperlipidemia, hypertension, and smoking 1

Mandatory Sequential Anti-Resorptive Therapy

Critical: Anabolic therapy MUST be followed by anti-resorptive treatment to prevent bone loss 7, 8, 3.

Sequential Therapy Options After Teriparatide/Romosozumab:

Option 1: Oral Bisphosphonates (Preferred for cost and experience)

• Alendronate or risedronate are first-choice agents due to low cost (generic availability), established efficacy, and extensive clinical experience 1
• Strongly recommended by the American College of Rheumatology for high/very high fracture risk patients 1
• Reduce vertebral fractures by 50-70%, nonvertebral by 20-30%, and hip fractures by ~40% 8

Option 2: Intravenous Zoledronic Acid

• Appropriate for patients with oral intolerance, malabsorption, dementia, or compliance concerns 1
• Administered annually, improving adherence 1

Option 3: Denosumab (Subcutaneous)

• Alternative for patients intolerant to bisphosphonates 1
• Administered every 6 months 8
• Critical warning: Pronounced rebound effect with clusters of vertebral fractures can occur from 7 months after the last injection if discontinued without transition to another anti-resorptive 8

Duration of Sequential Anti-Resorptive Therapy

• Bisphosphonates: typically 3-5 years initially, with consideration for drug holidays of 1-2 years after this period to minimize atypical femoral fracture risk 1, 8
• Continue longer if patient remains at high fracture risk 1
• Monitor bone mineral density with vertebral fracture assessment every 1-2 years 1

Non-Pharmacological Interventions (Concurrent with All Therapy)

All patients require optimization of:

• Calcium intake: 1000-1200 mg daily (dietary plus supplementation) 1
• Vitamin D: 800 IU daily minimum, titrated to maintain serum 25(OH)D ≥30-50 ng/mL 1
• Smoking cessation if applicable 1
• Alcohol limitation: ≤2 servings daily 1
• Weight-bearing or resistance training exercises 1
• Fall prevention strategies: given her multiple fractures, formal fall risk assessment and intervention are essential 1

Common Pitfalls to Avoid

• Do not combine teriparatide with bisphosphonates concurrently - combination therapy blunts the anabolic effect and provides no additional benefit 3
• Do not discontinue anabolic therapy without transitioning to anti-resorptive - this leads to rapid bone loss and increased fracture risk 7, 8
• Do not exceed 2-year lifetime exposure to teriparatide due to theoretical osteosarcoma risk 4
• Do not use romosozumab beyond 12 months as efficacy diminishes 7
• Do not start romosozumab without cardiovascular risk assessment 1
• If using denosumab as sequential therapy, never allow treatment gaps due to severe rebound vertebral fracture risk 8