Osteoclast Inhibition and Bone Formation

Mayo Clinic

Status and phase: Completed; Early Phase 1

Conditions: Aging; Bone Loss

Treatments: Drug: placebo; Drug: denosumab

Study type: Interventional

Funder types: Other

Identifiers

NCT02554695

15-002313

Details and patient eligibility

About

This protocol addresses: 1) How gene expression changes in bone cells are affected by aging? 2) Is aging associated with decreased signaling between bone cells? 3) How does treatment with the osteoporosis medication denosumab affect bone cell signaling?

Full description

This protocol collectively addresses the following goals: 1) What are the changes in gene expression in osteoblasts and osteocytes that lead to impaired bone formation with aging; 2) Since recent work from the investigators' group has demonstrated that osteoclasts produce a number of growth factors and cytokines (coupling factors) that enhance osteoblast proliferation and/or differentiation, is aging associated with reduced osteoclast coupling factor production; and 3) If osteoclasts are markedly reduced using the FDA-approved medication for osteoporosis, denosumab, how does that effect the quantity of coupling factors in the bone microenvironment and the target genes of these coupling factors in osteoblasts?

Enrollment: 81 patients

Sex: Female

Ages: 25 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• Inclusion Criteria:

  • normal premenopausal women aged 25-40 years
  • normal postmenopausal women aged 60-80 years
  • at least 5 yrs since their last menses
  • follicle stimulating hormone (FSH) > 20 IU/L

• Exclusion Criteria:

  • Abnormality in any of the screening laboratory studies
  • Presence of significant liver or renal disease
  • Malignancy (including myeloma)
  • Malabsorption
  • Diabetes
  • Hypoparathyroidism
  • Hyperparathyroidism
  • Acromegaly
  • Cushing's syndrome
  • Hypopituitarism
  • Severe chronic obstructive pulmonary disease
  • Undergoing treatment with any medications that affect bone turnover, including the following:

• adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)

• anticonvulsant therapy (within the previous year)

• pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)

• calcium supplementation of > 1200 mg/d (within the preceding 3 months)

• bisphosphonates (within the past 3 yrs)

• denosumab

• estrogen (E) therapy within the past year

• treatment with a selective E receptor modulator within the past year

• teriparatide within the past yr

  • Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm)
  • Recent (within the past 6 months) fracture
  • Serum 25-hydroxyvitamin D levels of < 20 ng/ml

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

81 participants in 3 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

single subcutaneous injection of placebo (normal saline)

Treatment:

Drug: placebo

Denosumab

Active Comparator group

Description:

single subcutaneous injection of denosumab 60 mg

Treatment:

Drug: denosumab

young normal premenopausal women

No Intervention group

Description:

no intervention