Drugs for Osteoporosis

Which mechanism of action distinguishes denosumab from bisphosphonates in the pharmacological management of osteoporosis?

Which bisphosphonate is preferred for intravenous administration in patients with severe osteoporosis who cannot tolerate oral formulations?

A 58-year-old postmenopausal woman presents with a 2-year history of progressive back pain and loss of height (4 cm). She denies trauma. Bone mineral density (BMD) T-score at the lumbar spine is −2.8 and at the femoral neck is −2.5. Serum calcium is 8.8 mg/dL, phosphate 3.5 mg/dL, alkaline phosphatase 65 U/L, and 25-hydroxyvitamin D is 28 ng/mL (low-normal). She has no contraindications to bisphosphonates. Which of the following is the most appropriate first-line pharmacological agent for this patient?

A 72-year-old woman with a 10-year history of osteoporosis has been on alendronate 70 mg weekly for 8 years. She now presents with severe left thigh pain and a pathological fracture of the left femur on imaging. Biochemical markers show suppressed bone turnover (P1NP 25 pg/mL, CTX 0.2 ng/mL; both very low). Serum calcium and phosphate are normal. What is the most likely diagnosis, and what is the recommended next step in management?