Clinical trial NCT02554695: Osteoclast Inhibition and Bone Formation
Official title: Effects of Age and Osteoclast Inhibition on Bone Formation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bone Loss
Aging
Keywords: adrenergic
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2015-09-18
Enrollment: 81
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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?

Detailed 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?

Eligibility 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

Primary outcomes:
measure: Gene expression changes in bone cells
timeFrame: 3 months
Secondary outcomes:
measure: Osteoclast-osteoblast coupling factor changes
timeFrame: 3 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Sundeep Khosla, MD
role: PRINCIPAL_INVESTIGATOR
References: