Low Bone Density
Conditions
Brief summary
Osteoporosis is an important health problem in the rapidly-aging demographic. Fragility fractures are devastating consequences of osteoporosis. The most common treatment approach in osteoporosis is inhibition of bone resorption with drugs like alendronate (ALN). Parathyroid hormone (PTH) stimulates bone formation and is the only anabolic drug available. Dual therapy with ALN and PTH is not as effective as single-drug therapy in preventing fracture. Bone progenitor cells (MSCs) are recruited to sites of bone remodeling when a growth factor called Transforming Growth Factor Beta (TGF-β1) is released from bone. Different osteoporosis medicines may have differing effects on this process. The effects of ALN versus PTH on bone progenitor recruitment in humans are unknown. This is a randomized, clinical trial of ALN, PTH, and calcium and vitamin D in post-menopausal women with low bone mass. Women will be treated for 3 months with ALN or PTH or calcium and vitamin D. Data collected will include bone biopsies for histomorphometry and micro computed tomography (µCT), bone marrow aspirates for molecular studies, peripheral blood to detect circulating bone progenitor cells and dual X-ray absorptiometry. The investigators hypothesize that in humans, PTH will 1) increase bone progenitor number, 2) enhance recruitment of bone progenitor cells to bone resorption sites, and 3) increase bone progenitor number in peripheral circulation. Furthermore, the investigators hypothesize that ALN treatment will have the opposite effect. Understanding the differences in bone progenitor cell activity and recruitment during osteoporosis therapy will provide a mechanistic rationale for effective use of PTH and anti-resorptive drugs in osteoporosis treatment.
Interventions
DRUGTeriparatide
20 mcg subq daily for 3 months
DRUGAlendronate
70 mg weekly for 3 months
DIETARY_SUPPLEMENTcalcium and vitamin D
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Post-menopausal women aged 50-80 years * T score \< -2.5 at lumbar spine, total hip or femoral neck on dual x-ray absorptiometry (DXA) OR T score \< -1.5 with a personal or family history of fracture
Exclusion criteria
* Previous use of bisphosphonates or Teriparatide; current estrogen therapy; any other osteoporosis therapy in the past 6 months * Metabolic bone disease other than osteoporosis * Body mass index (BMI) \< 18 * Weight \> 325 lbs * Current smoking or current alcohol use that exceeds 3 units of alcohol daily * Use of medications known to affect bone metabolism * Renal disease, history of kidney stones or hypercalciuria * Hypo- or hyperparathyroidism; hypo- or hypercalcemia * Serum vitamin D level \< 20 ng/dL * Refusal to adjust their dietary calcium to \<750mg (i.e. two servings per day of calcium rich food) * History of bone marrow or organ transplant * History of malignancy or radiation to the bone * History of esophageal stricture, dysmotility or severe reflux disease * Gastrointestinal malabsorption * Use of digoxin * Need for chronic anticoagulation therapy such as Coumadin, heparin or low molecular weight heparin or inability to discontinue anti-platelet medication * Bleeding diathesis; hemoglobin ≤ 12.5 g/dL (American Red Cross cut-off to donate blood) * International normalized ratio (INR) pro time \> 1.1 or activated partial thromboplastin time (APT) T ratio \> 1.2 * Platelets \< 150K/cu mm * Cellulitis at site of iliac crest * History of allergy to medications used in bone biopsy (demeclocycline, lidocaine) * Inability to understand and provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN). | up to 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Difference in Bone Formation as Assessed by Bone Histomorphometry on Bone Biopsy Between Treatment Groups | 3 months |
| Difference in Osteogenic Potential of Bone Marrow as Measure by Colony Forming Unit Osteoblast (CFU-Ob) Assays Between Treatment Groups | 3 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide teriparatide 20 mcg sq for 3 months
Teriparatide: 20 mcg subq daily for 3 months | 21 |
| Alendronate 70 mg po weekly for 3 months
Alendronate: 70 mg weekly for 3 months | 18 |
| Calcium and Vitamin D calcium 630 mg vitamin D 500 units daily for 3 months
calcium and vitamin D | 16 |
| Total | 55 |
Baseline characteristics
| Characteristic | Alendronate | Teriparatide | Total | Calcium and Vitamin D |
|---|---|---|---|---|
| Age, Customized 18 - 49 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 50 - 80 years | 18 Participants | 21 Participants | 55 Participants | 16 Participants |
| Age, Customized 81 - 100 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 18 participants | 21 participants | 55 participants | 16 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 55 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 18 | 0 / 16 |
| other Total, other adverse events | 2 / 21 | 0 / 18 | 1 / 16 |
| serious Total, serious adverse events | 0 / 21 | 0 / 18 | 0 / 16 |
Outcome results
Primary
The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN).
Time frame: up to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide | The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN). | 0.0000242 percent change in osteoprogenitor cells | Standard Deviation 0.0000283 |
| Alendronate | The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN). | 0.0000104 percent change in osteoprogenitor cells | Standard Deviation 0.0000231 |
| Calcium and Vitamin D | The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN). | -0.0000068 percent change in osteoprogenitor cells | Standard Deviation 0.0000449 |
Secondary
Difference in Bone Formation as Assessed by Bone Histomorphometry on Bone Biopsy Between Treatment Groups
Time frame: 3 months
Population: Collected bone biopsy samples were not analyzed and no data was generated. Therefore data was not collected.
Secondary
Difference in Osteogenic Potential of Bone Marrow as Measure by Colony Forming Unit Osteoblast (CFU-Ob) Assays Between Treatment Groups
Time frame: 3 months
Population: Collected osteoblast assay samples were not analyzed and no data was generated. Therefore data was not collected.