# Combined Anabolic Therapy in Postmenopausal Osteoporosis

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $587,840

## Abstract

Osteoporosis affects over 20 million Americans leading to 2 million fragility fractures and 300,000 hip
fractures every year. Among older adults with hip fracture, there is 5- to 8-fold increased risk of death
during the first 3 months post-fracture, and mortality 1-year post-fracture is approximately 25%. 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. Osteoporosis therapies fall into
two classes: 1) antiresorptive agents that inhibit bone breakdown and 2) anabolic agents that stimulate
new bone formation. Anabolic osteoporosis drugs (which include parathyroid hormone analogs such as
teriparatide and the sclerostin inhibitor, romosozumab) are among the most efficacious medications
available but do have limitations. Teriparatide, for example, not only stimulates bone formation but bone
resorption as well, resulting in increasing porosity of cortical bone. Additionally, the anabolic effects of
teriparatide wane after 6-12 months of treatment. Conversely, romosozumab has a unique mechanism of
action in that it both stimulates new bone formation and inhibits bone resorption. While its inhibition of
bone resorption is sustained, however, its stimulation of bone formation is even more transient than
teriparatide’s, lasting only 1-3 months. Developing a therapeutic regimen that stimulates bone formation
in a sustained and durable fashion, while also limiting bone resorption would represent a major advance
in osteoporosis management and greatly improve patient outcomes. Animal studies have suggested that
combining parathyroid hormone analogs with sclerostin inhibition results in greater gains in bone mass
than with either drug alone, but this approach has not yet been systematically assessed in patients with
osteoporosis. Thus, the aim of this study is to comparatively assess the therapeutic potential of
combined anabolic therapy versus the current standard-of-care single-drug approach in postmenopausal
women at high risk of fragility fracture. Specifically, in this proposal, we will test the hypothesis that in
postmenopausal women with osteoporosis, combined treatment with teriparatide and romosozumab will
improve skeletal parameters more than a standard treatment course of 12 months of romosozumab
alone. The successful completion of this study and confirmation of our hypothesis has the potential to
fundamentally shift the way established osteoporosis is treated and introduce a new concept in
osteoporosis management.

## Key facts

- **NIH application ID:** 10977280
- **Project number:** 1R21AR083567-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** BENJAMIN Z LEDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $587,840
- **Award type:** 1
- **Project period:** 2024-09-23 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977280

## Citation

> US National Institutes of Health, RePORTER application 10977280, Combined Anabolic Therapy in Postmenopausal Osteoporosis (1R21AR083567-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10977280. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*