1. Project Summary/Abstract
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.
Our 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 (1-43/49) with validation via the “gold standard” bone
biopsy and histomorphometry.
Our approach will be to enroll female patients 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 (1-43/49) 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.
Patients will be grouped according to turnover status. Low-turnover patients 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 patients (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. Our 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.