Novel Precision Medicine Approach to Treatment of Osteoporosis Based on Bone Turnover

  • STATUS
    Recruiting
  • End date
    Aug 31, 2026
  • participants needed
    60
  • sponsor
    Hartmut Malluche, MD
Updated on 25 May 2022
cancer
calcium
estrogen
breast cancer
vitamin d
osteoporosis
vitamin d deficiency
risedronate
alendronate
teriparatide
hypercalcemia

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 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.

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.

Details
Condition Age-Related Osteoporosis
Treatment Alendronate, Teriparatide
Clinical Study IdentifierNCT05151484
SponsorHartmut Malluche, MD
Last Modified on25 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosed Osteoporosis by DXA (BMD t-score ≤ -2.5 with or without fragility fractures)
Age ≥ 40 years
Females
White race
Normal levels of Vitamin D, and
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

Exclusion Criteria

Malignancy within the prior 5 years metastatic to bone or requiring chemotherapy
(except non-melanoma skin cancers or cervical carcinoma in situ)
Metabolic bone diseases (including osteomalacia, primary hyperparathyroidism and other
hypercalcemic disorders, Osteogenesis Imperfecta, Paget's disease, etc.)
Endocrinopathy (e.g., current hyperthyroidism, untreated hypothyroidism, Cushing's
syndrome
Other medical diseases (e.g., eating disorders, end stage liver, heart or lung
disease, intestinal malabsorption, chronic kidney disease stages 2-5D)
Any use of antiresorbers (e.g., alendronate, actonel, denosumab) or use within the
last two years of anabolic agents (e.g., teriparatide, abaloparatide)
Use within the prior year of glucocorticoids, hormone replacement therapy, calcitonin
selective estrogen receptor modulators or phenytoin
Pregnancy, desire to get pregnant, or nursing
Allergy to tetracycline
prior external beam or implant radiation therapy
use of non-aspirin anticoagulants that cannot be safely stopped for the biopsy
prisoners; and
radius BMD t-score ≤ -3.5
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