Mechanisms of Anabolic Osteoporosis Therapy

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

Study Overview

• Status: Recruiting
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Other: early versus late biopsy

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mackenzie Jordan; Phone Number: 617-726-6129; Email: MRJORDAN@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Mass General Brigham
      • Contact: Mackenzie Jordan; Email: MRJORDAN@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Early Biopsy; 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 clinical trial: 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.	Other: early versus late biopsy; early (3-6 weeks) versus late (6-8 months) biopsy
Active Comparator: Late Biopsy; 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 clinical trial: 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.	Other: early versus late biopsy; early (3-6 weeks) versus late (6-8 months) biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Osteoblast progenitor cell numbers	The investigators are testing the mechanistic hypothesis that romosozumab treatment increases osteoblast progenitor cell numbers at early, but not late, treatment time points.	3-6 weeks (early) versus 6-8 months (late)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Benjamin Leder, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Nutritional and Metabolic Diseases; Osteoporosis, Postmenopausal
• Other Study ID Numbers: 1P50AR080596-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No