Stem Cell Recruitment in Osteoporosis Therapy

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.

Study Overview

• Status: Terminated
• Conditions: Low Bone Density
• Intervention / Treatment: Drug: Teriparatide; Drug: Alendronate; Dietary supplement: calcium and vitamin D

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Suzanne Jan De Beur, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): August 7, 2020

Study Registration Dates

• First Submitted: August 1, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 3, 2012

Study Record Updates

• Last Update Posted (Actual): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Alendronate; Teriparatide
• Other Study ID Numbers: NA_00050448