What side effects are associated with this type of intervention?

Common treatments for osteoporosis, such as teriparatide (TPTD), bisphosphonates, and denosumab, have various side effects. Teriparatide can cause hypercalcemia, leg cramps, and dizziness. Bisphosphonates may lead to gastrointestinal issues, osteonecrosis of the jaw, and atypical femoral fractures. Denosumab is associated with hypocalcemia, infections, and rebound vertebral fractures upon discontinuation. Cinacalcet, when used with TPTD, can result in hypocalcemia due to its effects on calcium metabolism.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of osteoporosis, including teriparatide (TPTD), a parathyroid hormone analog that stimulates bone formation by activating PTH receptors on osteoblasts. Another approved drug is denosumab, which works by inhibiting osteoclast formation, thereby reducing bone resorption. Bisphosphonates like alendronate and zoledronic acid are also commonly used; they inhibit bone resorption by osteoclasts. While cinacalcet, a calcimimetic that activates calcium receptors in osteoblasts, is not specifically approved for osteoporosis, it is used to manage conditions like secondary hyperparathyroidism and has shown potential in improving bone density in related studies.

What other types of research exist?

Promising novel alternatives to TPTD+cinacalcet for osteoporosis treatment include romosozumab and denosumab. Romosozumab has shown significant improvements in BMD and reduction in vertebral and nonvertebral fractures. Denosumab, a RANKL inhibitor, has also demonstrated high efficacy in increasing BMD and reducing fracture risk. Both drugs are considered effective and have been highlighted in recent clinical trials for their benefits in osteoporosis management.

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Bone Anabolic Drug

Combination Therapy for Osteoporosis in Men (Osteo-Men Trial)

Phase 4

Waitlist Available

Led By Dolores M. Shoback, MD

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

DXA BMD T-score < or = -2.0 at either lumbar spine (LS), femoral neck (FN) or total hip (TH) sites; or DXA BMD T-score < or = -1.5 with at least one additional important clinical risk factor for osteoporotic fracture

Be older than 18 years old

Must not have

Testosterone therapy with dose change within last 12 months; or androgen deprivation therapy within 12 months

Hypercalcemia (albumin-corrected serum [Ca] >10.2 mg/dL), hypocalcemia (albumin-corrected serum [Ca] <8.8 mg/dL), elevated intact PTH level, or hypercalciuria (urinary Ca >300 mg/24 hours) at screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 weeks

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial tests a new combination of two drugs, Teriparatide and Cinacalcet, to treat osteoporosis in older men. Teriparatide builds bone mass, while Cinacalcet helps bone-forming cells work better. The study aims to see if using both drugs together improves bone strength more than using Teriparatide alone.

Who is the study for?

Men with osteoporosis can join this trial if they have a low bone mass score at certain sites in their body or additional risk factors for fractures. They must not have other metabolic bone diseases, severe heart issues, very high or low vitamin D levels, poorly controlled diabetes, recent cancer (except some skin cancers), and should not be on certain medications like steroids or drugs affecting calcium levels.

What is being tested?

The study is testing whether a combination of two drugs—Teriparatide (TPTD) and Cinacalcet—is more effective than TPTD alone in increasing bone density and strength in men with osteoporosis. Participants will receive either the drug combo or TPTD with a placebo for 11 months to compare effects on spine and hip bone density as well as blood markers of bone metabolism.

What are the potential side effects?

Possible side effects include nausea, dizziness due to changes in calcium levels; rare leg cramps or muscle spasms; injection site reactions from Teriparatide; and potential allergic reactions. Long-term use may affect bones differently but specific risks will be monitored closely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My bone density is low, indicating osteoporosis or I have a slightly higher bone density but with another risk factor for bone fractures.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have changed my testosterone therapy dose or had androgen deprivation therapy in the last year.

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My calcium levels are too high or too low, or I have high urine calcium.

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I have had cancer other than non-melanoma skin cancer in the last 5 years.

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I do not have a history of heavy drinking, liver disease, or poor liver function.

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I have a bone condition that is not osteoporosis.

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My kidney function is very low (stage 4 or 5 CKD).

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I have had radiation for bone issues, osteosarcoma, or bone spread of cancer.

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I have a history or risk of abnormal heart rhythms.

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I have a history of sudden blood pressure drops when standing up.

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I am not taking medications that affect CYP2D6 or CYP3A4 enzymes.

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My liver is not working well.

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My diabetes is not well-controlled (A1c >9%) or I am on thiazolidinedione treatment.

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I have heart problems that need medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on lumbar spine BMD in men with low bone mass

Secondary study objectives

Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on femoral neck BMD in men with low bone mass

Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on serum P1NP in men with low bone mass

Other study objectives

Pharmacodynamic responses to TPTD+cinacalcet and to TPTD+PBO in men with low bone mass

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: teriparatide (TPTD) + the calcimimetic cinacalcetExperimental Treatment4 Interventions

Combination arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a 30-mg tablet of cinacalcet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.

Group II: teriparatide (TPTD) + placeboPlacebo Group4 Interventions

Monotherapy arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a placebo tablet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vitamin D3

2011

Completed Phase 4

~3590

Cinacalcet

2010

Completed Phase 4

~6600

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Osteoporosis treatments work by either promoting bone formation or inhibiting bone resorption. Teriparatide (TPTD) is an anabolic agent that stimulates parathyroid hormone (PTH) receptors on osteoblasts, leading to increased bone formation and mass. Cinacalcet, a calcimimetic, activates calcium-sensing receptors on osteoblasts, further enhancing new bone formation. Bisphosphonates, such as alendronate, inhibit osteoclast-mediated bone resorption, thereby preserving bone density. Denosumab is a monoclonal antibody that inhibits RANKL, a key factor in osteoclast formation, reducing bone resorption. These mechanisms are crucial for osteoporosis patients as they help to restore and maintain bone strength, reducing the risk of fractures.

Cinacalcet Improves Bone Parameters Through Regulation of Osteoclast Endoplasmic Reticulum Stress, Autophagy, and Apoptotic Pathways in Chronic Kidney Disease-Mineral and Bone Disorder.Effects of Daily or Cyclic Teriparatide on Bone Formation in the Iliac Crest in Women on No Prior Therapy and in Women on Alendronate.Bone quality of the newest bone formed after two years of teriparatide therapy in patients who were previously treatment-naïve or on long-term alendronate therapy.