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

Trial Summary

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 data supports the effectiveness of the drug Romosozumab for osteoporosis?

Research shows that Romosozumab significantly increases bone mineral density (the strength of bones) and bone formation markers in patients with osteoporosis, making it more effective than other treatments like teriparatide. It also controls bone resorption (the process of breaking down bone), which enhances its ability to strengthen bones. ^{1 2 3 4 5}

Is romosozumab safe for humans?

Romosozumab has been studied for safety in treating osteoporosis, with research indicating it is generally safe but may have potential cardiovascular risks (related to the heart and blood vessels). ^{1 2 4 6 7}

How is the drug Romosozumab unique in treating osteoporosis?

Romosozumab is unique because it is a monoclonal antibody that both promotes bone formation and inhibits bone resorption by targeting sclerostin, a protein that regulates bone formation. This dual action leads to rapid and significant increases in bone mineral density, making it more effective than other treatments like bisphosphonates or parathyroid hormone analogs, and it is administered once a month through two injections. ^{1 5 8 9 10}

What is the purpose of this trial?

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

Research Team

Benjamin Leder, MD

Principal Investigator

Mass General Brigham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. [2019]

3. France pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]

4. Korea (South) 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Romosozumab/CDP7851 for the treatment of osteoporosis. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Utility of Romosozumab in the Management of Osteoporosis: Focus on Patient Selection and Perspectives. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Romosozumab: A Review in Postmenopausal Osteoporosis. [2021]

10. Austria pubmed.ncbi.nlm.nih.gov

Romosozumab: a novel bone anabolic treatment option for osteoporosis? [2020]