Osteoclast Inhibition and Bone Formation

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?

• 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