# Limited-duration anabolic therapy in postmenopausal osteoporosis

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $214,400

## Abstract

PROJECT SUMMARY
One in three women and one in five men will experience an osteoporotic fracture during their lifetime. Each
year over 300,000 people over the age of 65 are hospitalized for hip fractures which are associated with a 1-
year mortality rate of 20-30%. Current osteoporosis therapies reduce vertebral fracture risk in high-risk patients
but their ability to reduce the risk of non-vertebral fractures and hip fractures, specifically, is modest. The most
recently approved osteoporosis medication, romosozumab, has a unique mechanism of action in that it both
stimulates new bone formation and inhibits bone resorption. The timing of these actions, however, differs in
that its stimulation of new bone formation is transient, lasting only 1-3 months, whereas its inhibition of bone
resorption is sustained. Recently, romosozumab was shown to reduce the risk of both spine and non-spine
fractures more than the most widely used osteoporosis medication, alendronate. The recent FDA approval of
romosozumab, however, was accompanied by a “black box” warning as studies reported a significant
increased risk of major adverse cardiac events including stroke, myocardial infarction, and cardiovascular
death. Because romosozumab only transiently stimulates bone formation, we hypothesize that a much shorter
course of romosozumab, followed by a drug that potently but selectively inhibits bone resorption, would have
similar efficacy to the standard 12-month course of romosozumab. This shorter course of romosozumab would
be significantly more cost effective, more acceptable to patients (romosozumab is given as 2 injections every
month) and would likely reduce the romosozumab-mediated risk of major adverse cardiac events. In this
proposal, we will test our hypothesis via a single open-label proof-of-principle 12-month clinical trial in which
postmenopausal women at a high risk of fracture will receive either romosozumab for 3 months followed by the
antiresorptive medication, denosumab, for the 9 months or the standard 12-months treatment with
romosozumab. The primary endpoint of the study is the changes in dual-energy X-ray absorptiometry-derived
total hip bone mineral density from months 0-12. Changes in bone mineral density at other sites, biochemical
markers of bone metabolism, high-resolution QCT-derived compartmental volumetric bone mineral density,
trabecular bone microarchitecture, and cortical bone structure of the radius and tibia, as well as estimated
bone strength assessed by finite element analysis will be assessed as key secondary or exploratory endpoints.
The successful completion of the proposed study will define a safer, less expensive, and more rational
approach to the use of a promising new osteoporosis medication. In so doing, this study has the potential to
fundamentally change the way osteoporosis is treated, especially for those patients with severe and
established disease.

## Key facts

- **NIH application ID:** 10295401
- **Project number:** 1R21AR079718-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** BENJAMIN Z LEDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $214,400
- **Award type:** 1
- **Project period:** 2021-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295401

## Citation

> US National Institutes of Health, RePORTER application 10295401, Limited-duration anabolic therapy in postmenopausal osteoporosis (1R21AR079718-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10295401. Licensed CC0.

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