Alendronate + Exercise for Osteoporosis

(BEACON Trial)

Recruiting at 2 trial locations

Overseen By Christa Todoroff Calderone, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must not be taking: Oral steroids, Insulin, Biotin, others

Disqualifiers: Osteoporosis, Uncontrolled diabetes, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 12 months

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find ways to reduce bone loss in older adults who are losing weight. It will test whether combining alendronate (a bisphosphonate) with exercise or using them separately is effective. The trial includes four groups: some will do resistance training with the medication, some will take the medication without exercise, and others will receive a placebo (a pill with no active medicine) with or without exercise. Suitable participants have low bone mass and are currently receiving regular dental care.

As a Phase 4 trial, this research helps clarify how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain medications like oral steroids, diabetes prescriptions, or osteoporosis medications, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that alendronate, a type of medication, is generally safe for treating osteoporosis. The FDA has approved it for this purpose, with studies confirming its safety for up to four years. However, some people might experience throat irritation if they don't remain upright for 30 minutes after taking it.

Regarding resistance training, studies indicate it safely supports bone health. Most research finds no negative effects and even improvements in bone health from exercise. When combined with weight loss, resistance training can help maintain strong bones.

Overall, both alendronate and resistance training are well-tolerated. However, as with any treatment or exercise plan, participants should follow guidelines and consult healthcare providers. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining alendronate, a bisphosphonate, with resistance training to tackle osteoporosis. Most treatments for osteoporosis, like other bisphosphonates or hormone therapies, focus solely on slowing bone loss. But this approach not only uses alendronate to strengthen bones chemically but also incorporates resistance training to physically enhance bone density and resilience. This dual method could potentially offer more comprehensive protection against fractures by improving bone strength through two distinct pathways. By integrating exercise, this treatment could also have added benefits for overall physical health and mobility.

What evidence suggests that this trial's treatments could be effective for minimizing bone loss in older adults with osteoporosis?

Research has shown that alendronate, a type of medication, effectively treats osteoporosis. It increases bone strength and reduces fracture risk, specifically lowering spine fracture risk by 61%. Resistance training, such as weightlifting, also significantly improves bone health by increasing bone strength, helping to prevent bone loss. In this trial, some participants will receive both alendronate and resistance training, while others will receive alendronate without resistance training, or resistance training with a placebo. Together, alendronate and resistance training offer a promising way to reduce bone loss during weight loss. ^{6 7 8 9 10}

Who Is on the Research Team?

Kristen M Beavers, PhD, MPH, RD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

Adults with a BMI over 30, or over 25 with a risk factor, who have low bone mass but not full-blown osteoporosis can join. They must be able to walk without assistance, get regular dental care, and commit to the study visits for up to two years.

Inclusion Criteria

I get dental check-ups at least once a year.

Community-dwelling

My bone density test shows I have low bone mass.

Exclusion Criteria

I need a quad cane or walker to move around.

Resides with someone who is currently participating in BEACON

History of mild cognitive impairment or dementia or evidence of cognitive impairment ((score <20) on Montreal Cognitive Assessment (MoCA))

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo a 12-month intervention of resistance training plus bone-loading exercises and bisphosphonate use, or placebo, to assess effects on bone mineral density.

12 months

Up to 9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of bone mineral density and other bone quality measures.

12 months

Regular assessments at baseline, month 6, and month 12

What Are the Treatments Tested in This Trial?

Interventions

• Bisphosphonate
• Placebo
• Resistance Training/Bone-Loading Exercise

Trial Overview

The trial is testing if bisphosphonates (a type of medication) and resistance training exercises can help minimize bone loss during weight loss in older adults. Participants will also explore the effects of caloric restriction on bone health.

How Is the Trial Designed?

Group I: Resistance Training (RT) + Bisphosphonate (BIS) Experimental Treatment 2 Interventions

Progressive Resistance Training (RT) and Bone-Loading Exercise \+ 70 mg/weekly dose alendronate

Group II: No RT + BIS Experimental Treatment 1 Intervention

No Resistance Training \+ 70 mg/weekly dose alendronate

Group III: No RT + Placebo (PL) Active Control 1 Intervention

No Resistance Training + Weekly Placebo

Group IV: RT + PL Active Control 2 Interventions

Progressive RT and Bone-Loading Exercise + Weekly Placebo

Bisphosphonate is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• High calcium levels in cancer patients
• Bone metastases

Approved in United States as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• Glucocorticoid-induced osteoporosis
• High calcium levels in cancer patients
• Bone metastases

Approved in Canada as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• High calcium levels in cancer patients
• Bone metastases

Approved in Japan as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• High calcium levels in cancer patients
• Bone metastases

Approved in China as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• High calcium levels in cancer patients
• Bone metastases

Approved in Switzerland as Bisphosphonates for:

• Osteoporosis
• Paget's disease
• High calcium levels in cancer patients
• Bone metastases

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A study involving 32 postmenopausal women confirmed that a new intramuscular clodronate formulation (200 mg every two weeks) is bioequivalent to the standard formulation (100 mg weekly), meaning they work similarly in the body.

Both formulations were well-tolerated, with minimal side effects, suggesting that the less frequent dosing of the 200 mg formulation could improve patient adherence to osteoporosis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and tolerability of i.m. disodium clodronate 200 mg/lidocaine 1%, given twice monthly, in comparison with i.m. disodium clodronate 100 mg/lidocaine 1%, given weekly, in healthy postmenopausal female patients. Radicioni, M., Cremonesi, G., Baraldi, E., et al.[2013]

Cyclical clodronate therapy (200 mg IV every 3 weeks) significantly increased bone mineral density (BMD) by 5.69% over 6 years in 235 postmenopausal women with osteoporosis, while control patients experienced a decrease in BMD of -1.47%.

The therapy was well-tolerated and led to a significant reduction in new vertebral fractures from year 3 onward, particularly in patients who were fracture-free at the start, indicating its effectiveness in preventing further bone damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclical intravenous clodronate in postmenopausal osteoporosis: results of a long-term clinical trial. Filipponi, P., Cristallini, S., Rizzello, E., et al.[2019]

In a study involving 297 postmenopausal women with osteoporosis, a daily dose of 10 mg alendronate for 1 year resulted in significant increases in bone mineral density (BMD) at key sites: 5.6% at the lumbar spine, 3.6% at the trochanter, and 2.6% at the femoral neck, all significantly greater than the placebo group.

The treatment was found to be generally well tolerated, with no significant differences in adverse events or laboratory abnormalities compared to the placebo group, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled multicenter study of oral alendronate in postmenopausal osteoporotic women. FOSIT-Study-Group. Fosamax International Trial. Felsenberg, D., Alenfeld, F., Bock, O., et al.[2019]

Bisphosphonates, such as risedronate, have shown strong efficacy in preventing bone loss in postmenopausal women, with a study indicating that a daily dose of 5 mg completely prevented bone loss compared to a placebo.

New bisphosphonates like ibandronate and zoledronate are being developed with promising results, including significant increases in spinal bone mass and normalization of serum alkaline phosphatase in over 70% of patients, providing alternative treatment options for those intolerant to oral bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New bisphosphonates in the treatment of bone diseases. Gatti, D., Adami, S.[2022]

Alendronate is an effective treatment for osteoporosis in postmenopausal women, significantly reducing the risk of vertebral and nonvertebral fractures, as shown in large randomized controlled trials lasting up to 3 years.

The drug works by inhibiting osteoclast activity, which helps prevent bone loss without increasing the risk of osteomalacia, making it a safe option for increasing bone mass in women with osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug clinics. The drug of the month. Alendronate (Fosamax)]. Scheen, AJ.[2015]

The most important outcome for osteoporosis therapies is the reduction in fracture risk, rather than just changes in bone mineral density, highlighting a shift in focus for treatment effectiveness.

Among the bisphosphonates, alendronate and risedronate have shown the strongest evidence for reducing both vertebral and non-vertebral fractures, making them key options in osteoporosis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing osteoporotic fractures with bisphosphonates: a review of the efficacy and tolerability. Masud, T., Giannini, S.[2019]

Alendronate, clodronate, and etidronate have been shown to effectively reduce bone turnover and increase bone mineral density in postmenopausal women with osteoporosis, with alendronate and etidronate also demonstrating a reduction in osteoporotic fracture incidence in multicenter studies.

Safety concerns have been noted, particularly with alendronate, which may cause severe esophageal damage if not taken as directed, while etidronate has not shown significant side effects like osteomalacia at recommended doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonates and osteoporosis treatment in Italy. Gennari, C., Reginster, JY.[2019]

In a study of 210,144 women aged 65 and older, alendronate and risedronate significantly reduced fracture incidence over 12 months, with reductions of up to 57% at vertebral sites, indicating their effectiveness in preventing fractures in clinical practice.

Ibandronate showed a lower reduction in fracture incidence (31% at vertebral sites) and was prescribed to a younger cohort with fewer prior fractures, suggesting differences in patient risk profiles may influence the effectiveness of these bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal change in clinical fracture incidence after initiation of bisphosphonates. Abelson, A., Ringe, JD., Gold, DT., et al.[2021]

In a study of 186 women with postmenopausal osteoporosis, generic alendronate showed significantly lower increases in bone mineral density (BMD) compared to branded alendronate (Fosamax®) and branded risedronate (Actonel®) after one year, suggesting that the generic may be less effective.

Patients taking generic alendronate also had lower treatment persistence (68%) compared to those on branded medications (84% for Fosamax® and 94% for Actonel®), which may be linked to a higher incidence of gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Ringe, JD., Möller, G.[2021]

In a study of 74 asthmatic patients on long-term corticosteroid therapy, clodronate significantly increased bone mineral density (BMD) in the lumbar spine and femoral neck, particularly at higher doses of 1600 mg and 2400 mg per day.

Clodronate was effective in preventing bone loss, but the 2400 mg dose was associated with gastric irritation as a common side effect, highlighting the need to balance efficacy with tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clodronate is effective in preventing corticosteroid-induced bone loss among asthmatic patients. Herrala, J., Puolijoki, H., Liippo, K., et al.[2019]

Bisphosphonates are generally safe and well-tolerated for treating osteoporosis, with the most common side effects being gastrointestinal discomfort and flu-like symptoms, while serious adverse events are rare.

Skeletal complications like osteonecrosis of the jaw and atypical fragility fractures are infrequent compared to the risk of osteoporotic fractures, suggesting that the benefits of bisphosphonates often outweigh these risks, especially in patients with a similar fracture risk as those in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of bisphosphonates. Abrahamsen, B.[2022]

Oral bisphosphonates, commonly used for osteoporosis, can cause various adverse events including gastrointestinal issues, musculoskeletal pain, and osteonecrosis of the jaw, while intravenous bisphosphonates are linked to similar issues but with added risks of renal toxicity.

The severity and frequency of adverse events from bisphosphonates are often related to the dosage and potency of the medication, highlighting the need for careful management in their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-associated adverse events. Papapetrou, PD.[2022]

Alendronate, a bisphosphonate recently approved for postmenopausal osteoporosis, effectively increases bone mineral density and reduces the risk of new fractures, making it a key treatment option.

When taken correctly (10 mg per day with at least 6 oz of water 30 minutes before food), alendronate generally has a good safety profile with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alendronate: a bisphosphonate for treatment of osteoporosis. Kirk, JK., Spangler, JG.[2013]

Clodronate, a bisphosphonate, has been shown to significantly reduce the incidence of vertebral fractures after 4 years of treatment, particularly in patients at higher fracture risk, making it an effective option for osteoporosis and related bone conditions.

The drug is safe and well-tolerated, with flexible dosing strategies that can be tailored to individual fracture risk and pain severity, promoting better adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clodronate news of efficacy in osteoporosis. Nardi, A., Ventura, L., Cozzi, L., et al.[2020]

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