Clinical trial NCT05688969: Mechanisms of Anabolic Osteoporosis Therapy
Official title: Mechanisms of Anabolic Osteoporosis Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoporosis, Postmenopausal
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2023-01-18
Enrollment: 16
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 allocation
Primary purpose: OTHER

Brief summary: The aim of this study is to investigate the effect of romosozumab on bone cells during early and late phases of treatment.

Detailed description: 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.

Eligibility criteria: 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:

1. Female aged \> 45 years
2. Postmenopausal by either of the following criteria:

   1. \> 36 since last spontaneous menses
   2. \> 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.

Primary outcomes:
measure: Osteoblast progenitor cell numbers
timeFrame: 3-6 weeks (early) versus 6-8 months (late)
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Mass General Brigham
state: Massachusetts
Study officials:
affiliation: Mass General Brigham
name: Benjamin Leder, MD
role: PRINCIPAL_INVESTIGATOR
References: