Age-Related OsteoporosisPhase 4NCT05151484
Novel Precision Medicine Approach to Treatment of Osteoporosis Based on Bone Turnover
A Phase 4 study testing Teriparatide and Alendronate in people with Age-Related Osteoporosis, run by Madhumathi Rao at 1 site in United States.
Trial summary
Osteoporosis affects 24.5% of women over 65 and results in fracture-related hospital admissions exceeding those of heart attacks, strokes and breast cancer combined. Current treatment options do not account for differences between age-related and estrogen deficiency related osteoporosis, because of the need for bone… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Age-Related Osteoporosis
- What is being tested?
- Teriparatide and Alendronate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2022to 31 Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed Osteoporosis by DXA (BMD t-score ≤ -2.5 with or without fragility fractures)
- Treatment naive with respect to with anabolic or antiresorptive bone drugs.
- Premenopausal, menopausal, and post-menopausal females.
- 45 years old and older.
- Presence or absence of diabetes
- Normal levels of Vitamin D
- Absence of all exclusion criteria on clinical workup
- Patients diagnosed as osteoporotic due to the presence of fragility fractures, but without osteoporotic t-scores, will not be included because they would require fractures as a study endpoint which would entail a multi-center approach. Moreover, abnormal bone quality has been shown to be present in these patients, which requires bone histology for assessment.
Who cannot join
- Pregnant or trying to become pregnant or are breastfeeding.
- Participation in a study of an investigational drug during the past 30 days.
- Treatment with anabolic or antiresorptive bone drugs.
- Use of systemic anticoagulation (blood thinner)
- Planned or anticipated oral surgery within the next 12 months.
- Allergy to the antibiotics demeclocycline or tetracycline.
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- Planning to move out of the area within 18 months of the study.
- Inability to stand or sit upright for at least 30 minutes.
- Chronic alcoholism and/or drug addiction.
- Prior radiation therapy (external beam or implant radiation) involving the skeleton (only if randomized to the bone forming drug (anabolic Forteo®)).
- Systemic illnesses or organ diseases that may affect bone (except type 1 or type 2 Diabetes Mellitus).
- Clinical condition that may limit study participation (e.g., heart diseases (unstable angina), lung diseases (severe COPD), other infections).
- Abnormalities of the esophagus (tube connecting the mouth to the stomach) which delay esophageal emptying such as stricture (narrowing) or achalasia (a condition that prevents normal swallowing).
- Have other bone diseases that are not linked to age or menopause.
- Have a history of malignancy (cancer), not including non-melanoma skin cancer.
- Vitamin D (Calcidiol) level below the normal range (below 20ng/mL).
- AFTER RANDOMIZATION: If randomized to Group 1 Teriparatide and radius BMD t-score is less than -3.5 and does not sign consent to continue in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Osteoporosis affects 24.5% of women over 65 and results in fracture-related hospital admissions exceeding those of heart attacks, strokes and breast cancer combined. Current treatment options do not account for differences between age-related and estrogen deficiency related osteoporosis, because of the need for bone biopsies for determination. This study will establish a paradigm-shifting individualized treatment protocol for age-related osteoporosis and a non-invasive method for its determination, thereby reducing the major health problems and enormous burden on society and the elderly related to this disease.
Read the detailed description
Osteoporosis is a health problem of major proportions. It affects more than 40 million Americans and results in more than 2 million fractures annually among Medicare patients alone. Hospital admissions for osteoporotic fractures exceed those of heart attacks, strokes and breast cancer combined. Osteoporosis is commonly considered a disease associated with menopause. This estrogen deficiency related bone loss is characterized by high bone turnover with increased resorption without commensurate changes in bone formation. It is in contrast to age-related bone loss, which starts as early as in the fourth decade of life and continues with increasing age. Age-related bone loss is usually associated with lower bone turnover and decreased bone formation is the main abnormality. Current therapies do not address age-related bone loss and the special needs of the age-related osteoporosis population is currently ignored. This is to a great degree due to difficulties associated with the bone biopsy necessary for determination of bone turnover status. Thus, the current standard of care relies on starting with an antiresorber, which is less effective in age-related osteoporosis, and in fact impedes the effectiveness in this population of the appropriate anabolic medication.
The investigators study seeks to achieve two specific aims: Aim 1) to establish a novel precision medicine approach to treatment of age-related osteoporosis based on recognition of low bone turnover and initial treatment with anabolics, and Aim 2) to find a non-invasive method for diagnosing low bone turnover in osteoporotic patients by measurements of serum carboxylated osteocalcin with validation via the "gold standard" bone biopsy and histomorphometry.
The investigators approach will be to enroll female participants who have been diagnosed with osteoporosis in a prospective, proof of concept study. Patients will undergo bone biopsy and blood draws at baseline. Bone turnover status will be assessed employing histomorphometry. In addition, blood levels of carboxylated osteocalcin will be measured in order to determine their validity - alone or in combination with other bone markers - for diagnosing low bone turnover prevailing in age-related bone loss.
Participants will be grouped according to turnover status. Low-turnover participants will be randomized (1:1) either to treatment with the anabolic teriparatide (Group 1) or with the standard of care antiresorber alendronate (Group 2) for one year. In order to provide the necessary comparison group for the non-invasive assessment of turnover, normal-high turnover participants (Group 3) will be treated with standard of care alendronate for one year. At baseline and at one-year bone mineral density measurements will be performed by DXA and 1-year changes in BMD will be compared between groups. The investigators central hypothesis is that low turnover, age-related osteoporosis needs to be diagnosed and treated differently from estrogen deficiency related osteoporosis. The results will provide a paradigm shift in the treatment of osteoporosis.
- Conditions
- Age-Related Osteoporosis
- Being tested
- Teriparatide, Alendronate
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeriparatideDrug
Participants will receive 20 μg teriparatide per day via subcutaneous injections. Participants, and if needed a caregiver, will be trained in the subcutaneous administration of teriparatide according to the manufacturer's guidelines. The investigators will measure serum calcium, BSAP and TRAP-5b levels via blood draws at quarterly monitoring visits. If BSAP or TRAP-5b do not increase compared to baseline or decrease after any quarter, participants will be contacted and correct administration will be reviewed. Serum calcium is measured for safety to avoid hypo- and hypercalcemia. Participants will also be given a daily dose of Vitamin D of 800 IUs to prevent development of Vitamin D deficiency.
AlendronateDrug
Participants will receive 70 mg alendronate p.o. once per week. Participants will be carefully instructed to follow the manufacturer's recommendations for administration. Compliance will be assessed by measurement of the bone turnover markers BSAP and TRAP-5b from blood drawn at quarterly monitoring visits. These markers have been shown to be useful for assessment of turnover changes with treatment. If these markers do not decrease compared to baseline or rise after any quarter, participants will be contacted and correct administration will be reviewed. Participants will also be given a daily dose of Vitamin D of 800 IUs to prevent development of Vitamin D deficiency.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 Low Turnover | Active comparator | Teriparatide (anabolic) For 1 Year Receives: Drug: Teriparatide |
| Group 2 Low Turnover | Active comparator | Standard of Care - Control:
Treated with Alendronate (antiresorber) For 1 Year Receives: Drug: Alendronate |
| Group 3 Normal-High Turnover | Active comparator | Standard of Care Treatment with Alendronate (antiresorber) For 1 Year Receives: Drug: Alendronate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mineral Bone Density of the lumbar spine
Percent change in mineral bone density absolute values of the lumbar spine measured by DXA at baseline and at one year.
Measured: 1 Year
Measure of serum osteocalcin levels to predict bone turnover
Diagnostic Utility of serum osteocalcin level measurements by ELISA at baseline and at one year to predict bone turnover. Area under the receiver operating characteristic curve analysis will be used to determine the discriminative power of osteocalcin levels for determination of low versus non-low bone turnover.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2021
- Study start21 Mar 2022
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age-Related OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Madhumathi Rao
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Madhumathi Rao, University of Kentucky
- Investigators
- Madhumathi Rao, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05151484
- Sponsor's protocol ID
- 70781
- Other IDs
- R01AG072797
- Status last verified
- May 2026
- First submitted
- 17 Nov 2021
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Precision Medicine Approach to Treatment of Osteoporosis Based on Bone Turnover
- ClinicalTrials.gov ID
- NCT05151484
- Acronym / sponsor ID
- 70781
- Conditions
- Age-Related Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Madhumathi RaoUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 21 Mar 2022 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 9 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Osteoporosis affects 24.5% of women over 65 and results in fracture-related hospital admissions exceeding those of heart attacks, strokes and breast cancer combined. Current treatment options do not account for differences between age-related and estrogen deficiency related osteoporosis, because of the need for bone biopsies for determination. This study will establish a paradigm-shifting individualized treatment protocol for age-related osteoporosis and a non-invasive method for its determination, thereby reducing the major health problems and enormous burden on society and the elderly related to this disease.
Detailed description
Osteoporosis is a health problem of major proportions. It affects more than 40 million Americans and results in more than 2 million fractures annually among Medicare patients alone. Hospital admissions for osteoporotic fractures exceed those of heart attacks, strokes and breast cancer combined. Osteoporosis is commonly considered a disease associated with menopause. This estrogen deficiency related bone loss is characterized by high bone turnover with increased resorption without commensurate changes in bone formation. It is in contrast to age-related bone loss, which starts as early as in the fourth decade of life and continues with increasing age. Age-related bone loss is usually associated with lower bone turnover and decreased bone formation is the main abnormality. Current therapies do not address age-related bone loss and the special needs of the age-related osteoporosis population is currently ignored. This is to a great degree due to difficulties associated with the bone biopsy necessary for determination of bone turnover status. Thus, the current standard of care relies on starting with an antiresorber, which is less effective in age-related osteoporosis, and in fact impedes the effectiveness in this population of the appropriate anabolic medication.
The investigators study seeks to achieve two specific aims: Aim 1) to establish a novel precision medicine approach to treatment of age-related osteoporosis based on recognition of low bone turnover and initial treatment with anabolics, and Aim 2) to find a non-invasive method for diagnosing low bone turnover in osteoporotic patients by measurements of serum carboxylated osteocalcin with validation via the "gold standard" bone biopsy and histomorphometry.
The investigators approach will be to enroll female participants who have been diagnosed with osteoporosis in a prospective, proof of concept study. Patients will undergo bone biopsy and blood draws at baseline. Bone turnover status will be assessed employing histomorphometry. In addition, blood levels of carboxylated osteocalcin will be measured in order to determine their validity - alone or in combination with other bone markers - for diagnosing low bone turnover prevailing in age-related bone loss.
Participants will be grouped according to turnover status. Low-turnover participants will be randomized (1:1) either to treatment with the anabolic teriparatide (Group 1) or with the standard of care antiresorber alendronate (Group 2) for one year. In order to provide the necessary comparison group for the non-invasive assessment of turnover, normal-high turnover participants (Group 3) will be treated with standard of care alendronate for one year. At baseline and at one-year bone mineral density measurements will be performed by DXA and 1-year changes in BMD will be compared between groups. The investigators central hypothesis is that low turnover, age-related osteoporosis needs to be diagnosed and treated differently from estrogen deficiency related osteoporosis. The results will provide a paradigm shift in the treatment of osteoporosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 Low Turnover | Active comparator | Drug: TeriparatideTeriparatide (anabolic) For 1 Year |
| Group 2 Low Turnover | Active comparator | Drug: AlendronateStandard of Care - Control: Treated with Alendronate (antiresorber) For 1 Year |
| Group 3 Normal-High Turnover | Active comparator | Drug: AlendronateStandard of Care Treatment with Alendronate (antiresorber) For 1 Year |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosed Osteoporosis by DXA (BMD t-score ≤ -2.5 with or without fragility fractures)
- Treatment naive with respect to with anabolic or antiresorptive bone drugs.
- Premenopausal, menopausal, and post-menopausal females.
- 45 years old and older.
- Presence or absence of diabetes
Key exclusion criteria (17 listed)
- Pregnant or trying to become pregnant or are breastfeeding.
- Participation in a study of an investigational drug during the past 30 days.
- Treatment with anabolic or antiresorptive bone drugs.
- Use of systemic anticoagulation (blood thinner)
- Planned or anticipated oral surgery within the next 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriparatideParticipants will receive 20 μg teriparatide per day via subcutaneous injections. Participants, and if needed a caregiver, will be trained in the subcutaneous administration of teriparatide according to the manufacturer's guidelines. The investigators will measure serum calcium, BSAP and TRAP-5b levels via blood draws at quarterly monitoring visits. If BSAP or TRAP-5b do not increase compared to baseline or decrease after any quarter, participants will be contacted and correct administration will be reviewed. Serum calcium is measured for safety to avoid hypo- and hypercalcemia. Participants will also be given a daily dose of Vitamin D of 800 IUs to prevent development of Vitamin D deficiency. | Drug | Group 1 Low Turnover |
| AlendronateParticipants will receive 70 mg alendronate p.o. once per week. Participants will be carefully instructed to follow the manufacturer's recommendations for administration. Compliance will be assessed by measurement of the bone turnover markers BSAP and TRAP-5b from blood drawn at quarterly monitoring visits. These markers have been shown to be useful for assessment of turnover changes with treatment. If these markers do not decrease compared to baseline or rise after any quarter, participants will be contacted and correct administration will be reviewed. Participants will also be given a daily dose of Vitamin D of 800 IUs to prevent development of Vitamin D deficiency. | Drug | Group 2 Low Turnover, Group 3 Normal-High Turnover |
Primary outcome
Mineral Bone Density of the lumbar spine
Time frame: 1 Year
Percent change in mineral bone density absolute values of the lumbar spine measured by DXA at baseline and at one year.
Measure of serum osteocalcin levels to predict bone turnover
Time frame: 1 Year
Diagnostic Utility of serum osteocalcin level measurements by ELISA at baseline and at one year to predict bone turnover. Area under the receiver operating characteristic curve analysis will be used to determine the discriminative power of osteocalcin levels for determination of low versus non-low bone turnover.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Madhumathi Rao, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Teriparatide and Alendronate in people with Age-Related Osteoporosis, run by Madhumathi Rao at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mineral Bone Density of the lumbar spine (time frame: 1 Year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.