Alendronate + Teriparatide for Osteoporosis

Overseen By Madhumathi Rao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Madhumathi Rao

Must not be taking: Anticoagulants, Anabolic drugs

Disqualifiers: Pregnancy, Oral surgery, Cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks a better way to treat osteoporosis, particularly in aging individuals, without requiring bone biopsies. Researchers are testing two treatments: Alendronate (also known as Fosamax, Fosamax Plus D, or Binosto), which slows bone breakdown, and Teriparatide (also known as Forteo), which helps build bone. Participants will be divided into groups based on their bone turnover rates and will receive different treatments for a year. Women diagnosed with osteoporosis who have not previously received bone-specific drugs may be suitable candidates for this study. As a Phase 4 trial, the treatments are already FDA-approved and have proven effective, allowing researchers to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires that participants have not been treated with anabolic or antiresorptive bone drugs before. If you are currently taking these types of medications, you would need to stop them to participate.

What is the safety track record for Alendronate and Teriparatide?

Previous studies have shown that teriparatide is safe for treating osteoporosis, particularly in patients at high risk of fractures. Some side effects, such as pain, muscle spasms, and nausea, are common with osteoporosis treatments and are usually manageable. Importantly, teriparatide no longer carries a warning about the risk of osteosarcoma, allowing its use without a specific time limit.

Research has shown that alendronate is a well-known treatment for osteoporosis. It is generally well-tolerated, though some patients might experience stomach discomfort. This medication is widely used and considered safe for long-term management of osteoporosis.

Overall, both teriparatide and alendronate have been extensively studied and are known to be safe for treating osteoporosis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining Alendronate and Teriparatide for osteoporosis because these treatments work in complementary ways. While Alendronate is an antiresorptive agent that slows bone loss by inhibiting the cells that break down bone, Teriparatide is anabolic and stimulates new bone growth by activating bone-forming cells. This dual-action approach has the potential to not only preserve existing bone but also build new bone, offering a more comprehensive strategy than using either treatment alone. This combination could provide a significant advantage in managing osteoporosis, particularly for patients with varying bone turnover rates.

What evidence suggests that this trial's treatments could be effective for osteoporosis?

Research has shown that teriparatide, which participants in this trial may receive, effectively treats osteoporosis by reducing the risk of new spine fractures by up to 65% and increasing bone strength by 9%. Studies have also found that it lowers the chances of fractures in the spine, hips, and other areas over time. Teriparatide improves quality of life and reduces pain compared to treatments like alendronate.

For alendronate, another treatment option in this trial, research indicates that it slows bone loss in people with osteoporosis. It is a common treatment because it maintains bone strength and reduces fracture risk. Both treatments have successfully managed osteoporosis, each working differently to strengthen bones and prevent fractures. ^{2 6 7 8 9}

Who Is on the Research Team?

Madhumathi Rao, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for women aged 45 and older with diagnosed osteoporosis (bone density score ≤ -2.5), who haven't used bone drugs before, regardless of menopause status or diabetes presence. Exclusions include chronic substance abuse, certain systemic illnesses affecting bones, pregnancy, recent participation in other drug trials, planned surgeries within a year, inability to sit/stand for 30 minutes, and plans to move away soon.

Inclusion Criteria

Absence of all exclusion criteria on clinical workup

I am 45 years old or older.

I have been diagnosed with osteoporosis based on a DXA scan.

Exclusion Criteria

I have bone conditions not related to aging or menopause.

I cannot sit or stand up straight for 30 minutes.

I plan to have oral surgery in the next year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo bone biopsy and blood draws to assess bone turnover status

1 week

1 visit (in-person)

Treatment

Participants receive either teriparatide or alendronate based on bone turnover status for one year

52 weeks

Regular visits (in-person) for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Alendronate
• Teriparatide

Trial Overview

The study tests Alendronate versus Teriparatide as treatments for osteoporosis in postmenopausal women. It aims to tailor treatment based on non-invasive determination of age-related bone loss without needing biopsies—potentially revolutionizing how this common condition is managed.

How Is the Trial Designed?

Group I: Group 3 Normal-High Turnover Active Control 1 Intervention

Standard of Care Treatment with Alendronate (antiresorber) For 1 Year

Group II: Group 1 Low Turnover Active Control 1 Intervention

Teriparatide (anabolic) For 1 Year

Group III: Group 2 Low Turnover Active Control 1 Intervention

Standard of Care - Control: Treated with Alendronate (antiresorber) For 1 Year

Alendronate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fosamax for:

• Prevention and treatment of osteoporosis in postmenopausal women
• Treatment of osteoporosis in men

Approved in European Union as Fosamax for:

• Treatment of osteoporosis in postmenopausal women at risk of fracture
• Treatment of osteoporosis in men at risk of fracture

Approved in Canada as Fosamax for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of osteoporosis in men

Who Is Running the Clinical Trial?

Madhumathi Rao

Lead Sponsor

Hartmut Malluche, MD

Lead Sponsor

Trials

4

Recruited

710+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a systematic review of 6 trials with 618 postmenopausal osteoporosis patients, teriparatide significantly increased lumbar spine bone mineral density (BMD) compared to alendronate, particularly notable at 12 months of treatment.

However, teriparatide did not show a superior ability to reduce fracture risk compared to alendronate, indicating that while it may improve bone density, both treatments have similar safety profiles regarding fracture prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of teriparatide versus alendronate for treatment of postmenopausal osteoporosis: A meta-analysis of randomized controlled trials. Wang, YK., Qin, SQ., Ma, T., et al.[2021]

In a study of 64 patients who completed 2 years of teriparatide treatment, those who switched to denosumab experienced the greatest increase in bone mineral density (BMD) at both the lumbar spine (4.94%) and femoral neck (5.68%) after an additional 2 years.

Patients who stopped osteoporosis treatment after teriparatide showed a significant decline in BMD, increasing their risk of fragility fractures, highlighting the importance of continued treatment with antiresorptive drugs like denosumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of bone remodeling agents following teriparatide treatment. Burkard, D., Beckett, T., Kourtjian, E., et al.[2019]

Recombinant teriparatide (Forteo) is an effective anabolic treatment for osteoporosis, significantly improving bone mineral density and reducing fracture risk in various patient groups, including postmenopausal women and men with idiopathic or glucocorticoid-induced osteoporosis, over a treatment period of 11-21 months.

Teriparatide is generally well tolerated, but due to treatment duration limits and high costs, it is recommended primarily for patients at high fracture risk or those who do not respond well to other osteoporosis treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriparatide: a review of its use in osteoporosis. Blick, SK., Dhillon, S., Keam, SJ.[2021]

In a study of 203 postmenopausal women with osteoporosis over 18 months, teriparatide significantly increased bone mineral density (BMD) and markers of bone turnover, indicating its effectiveness in stimulating bone formation compared to alendronate, which suppresses bone remodeling.

At 18 months, teriparatide resulted in greater increases in areal and volumetric spine BMD (10.3% and 19.0%, respectively) compared to alendronate (5.5% and 3.8%), highlighting the different mechanisms of action between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. McClung, MR., San Martin, J., Miller, PD., et al.[2022]

Recombinant teriparatide (20 microg/day) is effective in increasing bone mineral density and reducing fracture risk in various osteoporosis patients, including postmenopausal women and men with idiopathic or hypogonadal osteoporosis, over a treatment period of 11-21 months.

The positive effects of teriparatide on bone health, including vertebral fracture prevention, continue even after treatment ends, making it a valuable option for high-risk osteoporosis patients, despite its high cost and treatment duration limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on teriparatide in osteoporosis. Blick, SK., Dhillon, S., Keam, SJ.[2016]

In a study involving 159 patients with femoral neck fractures, teriparatide did not show a significant improvement in reducing the need for revision surgery or enhancing radiographic fracture healing compared to placebo.

The safety profile of teriparatide was consistent with previous findings, as the rate of adverse events was similar between the teriparatide and placebo groups, indicating that it is safe for use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Teriparatide Improve Femoral Neck Fracture Healing: Results From A Randomized Placebo-controlled Trial. Bhandari, M., Jin, L., See, K., et al.[2019]

After one year of treatment with teriparatide, all groups of postmenopausal women with osteoporosis showed significant increases in lumbar spine bone mineral density (BMD), with the treatment-naïve group experiencing the highest increase of 8.4%.

The treatment-naïve group also showed a significant increase in total hip BMD, while the groups with prior antiresorptive treatment did not show any improvement in hip BMD, indicating that teriparatide may be more effective in patients who have not previously received osteoporosis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study. Minne, H., Audran, M., Simões, ME., et al.[2022]

In a study of 1,648 postmenopausal women with osteoporosis treated with teriparatide for up to 18 months, there was a significant 47% reduction in the odds of experiencing fragility fractures during the last 6 months compared to the first 6 months.

Patients also reported a notable decrease in back pain and improvements in health-related quality of life, with safety profiles aligning with existing prescribing information, indicating that teriparatide is effective and generally safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide: 18-month data from the European Forsteo Observational Study (EFOS). Langdahl, BL., Rajzbaum, G., Jakob, F., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

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sciencedirect.com

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4939987/

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Teriparatide has a favorable safety profile and is effective in the treatment of patients with osteoporosis at high risk of fracture in Japan.

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frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1391356/full

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For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S8756328225000043

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Romosozumab after treatment with daily or weekly teriparatide was relatively safe and more effective in patients with primary osteoporosis than in those with ...

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ccjm.org

ccjm.org/content/88/9/489

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Teriparatide (Forteo) no longer carries a boxed warning about the risk of osteosarcoma, and dosing is no longer limited to 24 months of lifetime use.