Mechanisms of Anabolic Osteoporosis Therapy

The investigators will perform paired iliac crest bone biopsies in postmenopausal women who meet standard romosozumab treatment indications and are being prescribed romosozumab by their treating physician. All study volunteers will have a bone biopsy procedure prior to starting therapy, and then an identical procedure at the contralateral side either 3-6 weeks ("early") or 6-8 months ("late") after starting therapy. This is not a randomized clinical trial testing the efficacy of a drug - the investigators will not be assigning volunteers to a specific osteoporosis therapy, though the investigators will randomize volunteers to either the early or late second biopsy.

Inclusion criteria

All postmenopausal women who are prescribed romosozumab by their treating physicians, meet the FDA-defined indication for romosozumab, and who are not at increased risk for a bone marrow aspirate or bone biopsy will be offered enrollment. The FDA approved indication for romosozumab is: "the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy." Volunteers must be:

• Female aged > 45 years
• Postmenopausal by either of the following criteria:

• > 36 since last spontaneous menses
• > 36 months since hysterectomy, plus serum FSH > 40 units / liter if < 60 years

Exclusion criteria

• renal disease (stage 4 CKD)
• elevated blood PTH (intact PTH > 77 pg/ml).
• serum 25-OH vitamin D < 20 ng/ml
• major psychiatric disease that in the opinion of the investigator would preclude the subject from providing adequate informed consent or completing the protocol procedures.
• excessive alcohol use or substance abuse that would preclude the subject from providing adequate informed consent or completing the protocol procedures.
• known congenital or acquired bone disease other than osteoporosis.
• exposure to oral bisphosphonates within the past 3 months, denosumab in the last 12 months, intravenous bisphosphonates within the past 24 months.
• exposure to estrogens, SERMs, or calcitonin, oral or parenteral glucocorticoids for more than 14 days in the past 2 months.
• any prior exposure to romosozumab.