Stem Cell Recruitment in Osteoporosis Therapy

NCT ID: NCT01656629

Last Updated: 2020-08-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2020-08-07

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.

Conditions

Low Bone Density

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

teriparatide

teriparatide 20 mcg sq for 3 months

Group Type: ACTIVE_COMPARATOR

Teriparatide

Intervention Type: DRUG

20 mcg subq daily for 3 months

Alendronate

70 mg po weekly for 3 months

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

70 mg weekly for 3 months

calcium and vitamin D

calcium 630 mg vitamin D 500 units daily for 3 months

Group Type: ACTIVE_COMPARATOR

calcium and vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Interventions

Teriparatide

20 mcg subq daily for 3 months

Intervention Type: DRUG

Alendronate

70 mg weekly for 3 months

Intervention Type: DRUG

calcium and vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suzanne Jan De Beur, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NA_00050448

Identifier Type: -

Identifier Source: org_study_id