Stem Cell Recruitment in Osteoporosis Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01656629
First received: August 1, 2012
Last updated: August 18, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention
Low Bone Density
Drug: Teriparatide
Drug: Alendronate
Dietary Supplement: calcium and vitamin D

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • The percent change in circulating osteoprogenitor cells as assessed by flow cytometry in the blood before and after treatment with PTH or ALN. [ Time Frame: up to 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference in bone formation as assessed by bone histomorphometry on bone biopsy between treatment groups [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Difference in osteogenic potential of bone marrow as measure by colony forming unit osteoblast (CFU-Ob) assays between treatment groups [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: August 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: teriparatide
teriparatide 20 mcg sq for 3 months
Drug: Teriparatide
20 mcg subq daily for 3 months
Active Comparator: Alendronate
70 mg po weekly for 3 months
Drug: Alendronate
70 mg weekly for 3 months
Active Comparator: calcium and vitamin D
calcium 630 mg vitamin D 500 units daily for 3 months
Dietary Supplement: calcium and vitamin D

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 PTH; current estrogen therapy; any other osteoporosis therapy in the past 6 months
  • Metabolic bone disease other than osteoporosis
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656629

Locations
United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
  More Information

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01656629     History of Changes
Other Study ID Numbers: NA_00050448 
Study First Received: August 1, 2012
Last Updated: August 18, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Vitamins
Vitamin D
Ergocalciferols
Calcium, Dietary
Alendronate
Teriparatide
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 30, 2016