Anabolic Therapy Timing for Osteoporosis

Overseen By Mackenzie Jordan

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Romosozumab

Must not be taking: Bisphosphonates, Denosumab, Estrogens, others

Disqualifiers: Renal disease, Psychiatric disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how romosozumab, an osteoporosis medication, affects bone cells in postmenopausal women with osteoporosis at different treatment stages. The study involves two groups: one will have a bone biopsy (a small sample taken from the bone) early in the treatment, and the other later, to assess how timing influences bone growth and health. It specifically seeks women already prescribed romosozumab due to a high fracture risk from osteoporosis, excluding those with complicating health issues like certain kidney problems or excessive alcohol use. As an unphased trial, this study allows participants to contribute to valuable research that may enhance osteoporosis treatment strategies.

Will I have to stop taking my current medications?

You may need to stop certain medications before joining the trial. Specifically, you should not have taken oral bisphosphonates in the past 3 months, denosumab in the last 12 months, or intravenous bisphosphonates in the past 24 months. Also, you should not have used estrogens, SERMs, calcitonin, or glucocorticoids for more than 14 days in the past 2 months.

What prior data suggests that romosozumab and biopsy procedures are safe for osteoporosis treatment?

Research has shown that romosozumab is a treatment for osteoporosis tested for safety in people. In some studies, women taking romosozumab had a slightly higher chance of heart-related problems compared to those taking alendronate, another osteoporosis drug. Specifically, 2.5% of participants experienced heart-related side effects with romosozumab, while 1.9% did with alendronate.

Some studies also reported deaths from any cause, with 1.5% of women in the romosozumab group experiencing this, compared to 1.1% in the alendronate group. Despite these concerns, romosozumab has greatly reduced the risk of new spine fractures and other bone breaks, making it a potentially helpful option for managing osteoporosis.

Participants should discuss these findings with their healthcare provider to understand the risks and benefits for their own health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to refine our understanding of the optimal timing for bone biopsies when using romosozumab, a treatment for osteoporosis. Unlike standard osteoporosis treatments that primarily include bisphosphonates or denosumab, romosozumab works by both increasing bone formation and decreasing bone resorption, thanks to its action on the sclerostin protein. This dual mechanism offers a unique advantage, potentially leading to stronger bones more quickly. The trial seeks to provide insights into how early or late interventions with romosozumab might affect bone structure, which could refine treatment strategies and improve outcomes for patients with osteoporosis.

What evidence suggests that romosozumab might be an effective treatment for osteoporosis?

Research has shown that romosozumab effectively treats osteoporosis. Studies have found that this treatment significantly improves bone strength in the spine, hip, and upper thigh over 12 months. Additionally, romosozumab reduces the risk of spine and other bone fractures in postmenopausal women. These findings strongly suggest that romosozumab can help strengthen bones and lower fracture risk for people with osteoporosis. ^{2 4 5 6 7}

Who Is on the Research Team?

Benjamin Leder, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for postmenopausal women over 45 with osteoporosis who are not at high risk for bone procedures and have been prescribed romosozumab. They mustn't have other bone diseases, recent use of certain hormones or steroids, major psychiatric conditions, low vitamin D levels, high PTH levels, prior romosozumab exposure, substance abuse issues, or severe kidney disease.

Inclusion Criteria

I am postmenopausal, with no period for over 3 years or had a hysterectomy with high FSH levels if I'm under 60.

I am eligible for romosozumab treatment according to FDA guidelines.

Not at increased risk for a bone marrow aspirate or bone biopsy

Exclusion Criteria

You drink too much alcohol or use drugs in a way that would make it hard for you to understand the study or follow the study rules.

I have previously been treated with romosozumab.

I haven't taken oral bisphosphonates in the last 3 months, denosumab in the last year, or IV bisphosphonates in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Biopsy

Participants undergo a bone biopsy procedure prior to starting romosozumab therapy

1 day

1 visit (in-person)

Early Treatment

Participants receive romosozumab therapy and undergo a second bone biopsy 3-6 weeks after starting therapy

3-6 weeks

1 visit (in-person)

Late Treatment

Participants continue romosozumab therapy and undergo a second bone biopsy 6-8 months after starting therapy

6-8 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Romosozumab

Trial Overview The study examines the effects of a medication called romosozumab on bone cells in women with osteoporosis. It compares results from early versus late treatment phases to understand how this drug works over time.

How Is the Trial Designed?

Group I: Late Biopsy Active Control 1 Intervention

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.

Group II: Early Biopsy Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Romosozumab is a highly effective treatment for osteoporosis, functioning as a monoclonal antibody that inhibits sclerostin, leading to increased bone mineral density (BMD) and superior results compared to traditional treatments like bisphosphonates and PTH analogs.

While romosozumab shows significant benefits in bone density and fracture risk reduction, it carries a black box warning for patients with recent myocardial infarction or stroke, indicating a need for caution and further research on its cardiovascular safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Romosozumab in the Management of Osteoporosis: Focus on Patient Selection and Perspectives. Lim, SY., Bolster, MB.[2022]

In a study of 148 postmenopausal osteoporosis patients, those who were treatment-naïve showed the greatest increase in bone mineral density (BMD) after 12 months of romosozumab treatment, with an 18.2% increase in lumbar spine BMD compared to lower increases in patients previously treated with bisphosphonates or other therapies.

The effectiveness of romosozumab in increasing BMD was significantly influenced by the type of prior treatment and early changes in bone turnover markers, indicating that these factors can help predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. Ebina, K., Tsuboi, H., Nagayama, Y., et al.[2021]

Romosozumab is an effective treatment for severe osteoporosis in postmenopausal women, significantly reducing vertebral and clinical fracture risk compared to placebo and oral alendronate in pivotal phase III trials involving monthly doses over 12 months.

The treatment not only increased bone mineral density significantly but also maintained these benefits even after transitioning to other osteoporosis therapies, indicating its potential as a valuable option for women at high risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: A Review in Postmenopausal Osteoporosis. Paik, J., Scott, LJ.[2021]

Romosozumab significantly reduces the incidence of new vertebral fractures in postmenopausal women with osteoporosis after just 12 months of treatment, showing strong efficacy compared to both placebo and active bisphosphonate controls.

However, there is a concerning numerical increase in cardiovascular events associated with romosozumab, suggesting it should be used cautiously, especially in patients with a history of cardiovascular issues or high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. Fixen, C., Tunoa, J.[2021]

In a study of 130 postmenopausal osteoporosis patients, those who were treatment-naïve showed the greatest increase in lumbar spine bone mineral density (BMD) after six months of romosozumab treatment, with a 13.6% increase compared to lower increases in patients previously treated with bisphosphonates, denosumab, or teriparatide.

The early changes in bone turnover markers, specifically PINP and TRACP-5b, were significant predictors of the increase in lumbar spine BMD, indicating that monitoring these markers could help assess treatment response to romosozumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. Ebina, K., Hirao, M., Tsuboi, H., et al.[2021]

Romosozumab significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 63% lower risk of new vertebral fractures and a 41% lower risk of hip fractures compared to other therapies, based on data from six randomized controlled trials involving over 5,600 participants.

The treatment also leads to substantial increases in bone mineral density (BMD) at key sites like the lumbar spine and hip, while demonstrating a good safety profile with no significant increase in adverse events compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. Liu, Y., Cao, Y., Zhang, S., et al.[2019]

Romosozumab significantly increases bone mineral density (BMD) in patients with osteoporosis, showing greater gains at the lumbar spine and hip compared to teriparatide after 12 months, making it an effective treatment option.

While romosozumab reduces fracture risk in high-risk postmenopausal women, it is associated with a higher incidence of serious cardiovascular events, so it should be avoided in patients with recent history of myocardial infarction or stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. Nealy, KL., Harris, KB.[2021]

In a study of 70 patients with severe osteoporosis, romosozumab significantly improved bone metabolism markers (TRACP 5b and P1NP) within 1-2 months of treatment, indicating its effectiveness in enhancing bone formation.

After 5-7 months of treatment, romosozumab led to a significant increase in bone density, specifically in the lumbar spine, demonstrating its potential as a dual-action therapy that both enhances bone formation and reduces bone resorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study. Inage, K., Orita, S., Eguchi, Y., et al.[2021]

Romosozumab, a monoclonal antibody targeting sclerostin, has shown rapid and significant increases in bone mineral density over two years, making it a promising anabolic therapy for osteoporosis.

This treatment not only boosts bone formation but also controls bone resorption, offering a unique advantage over existing therapies like teriparatide, and has been well tolerated in initial studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab/CDP7851 for the treatment of osteoporosis. Sim, IW., Ebeling, PR.[2019]

Romosozumab effectively increases bone mineral density and reduces fracture risk in osteoporosis patients, with clinical studies showing a 28-36% reduction in vertebral fractures and a 42% reduction in nonvertebral fractures.

While romosozumab is generally safe, with only about 5% of patients experiencing injection site reactions, there is a potential risk of cardiovascular side effects, although serious complications were not significantly higher than in the control group during phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: a novel bone anabolic treatment option for osteoporosis? Kerschan-Schindl, K.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12072299/

Real-World Evaluation of 12-Month Romosozumab ... Conclusions: This study demonstrated that 12 months of romosozumab treatment significantly improved BMD and bone turnover markers in ...

2. ucb.com ucb.com/newsroom/press-releases/article/global-data-show-real-world-effectiveness-of-romosozumab-for-patients-at-high-fracture-risk

Global data show real-world effectiveness of romosozumab ... Romosozumab was associated with significant improvements in bone mineral density (BMD) at 12 months versus baseline in lumbar spine, total hip and femoral neck ...

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04563-z

Romosozumab in osteoporosis: yesterday, today and ... The outcomes showed that romosozumab did not accelerate bone fracture healing regardless of the doses [82]. Concurrently, another phase 2 dose- ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1607948

Romosozumab Treatment in Postmenopausal Women with ... One year of romosozumab treatment in postmenopausal women with osteoporosis resulted in a lower risk of vertebral and clinical fractures than ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2214031X24000846

Treatment effects, adverse outcomes and cardiovascular ... In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39227560/

Cardiovascular Safety of Romosozumab Compared to ... Conclusion: Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with ...

7. tga.gov.au tga.gov.au/news/safety-updates/new-warnings-romosozumab-evenity-cardiovascular-risks

New warnings of romosozumab (Evenity) cardiovascular ... All-cause death occurred in 30 women (1.5%) in the romosozumab group and 22 women (1.1%) in the alendronate group. In the placebo-controlled ...