Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults

Seminal work on MK-677 (ibutamoren) in the elderly, integrating data from three randomized, double-blind, placebo-controlled trials conducted by the Merck research group — original manufacturer of the compound. The focus was to assess the impact of the oral GH secretagogue on bone turnover in a population with characteristic decline of the somatotropic axis.

The studies enrolled 187 elderly subjects aged ≥65 years, stratified between healthy and functionally impaired. Daily oral doses ranged from 10 mg to 25 mg, with duration of up to 9 weeks. The authors measured biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (telopeptides), as well as serum IGF-1 — key biomarker of GH axis activity.

Results were consistent across the studies: MK-677 elevated serum IGF-1 by 55-94% and increased osteocalcin by 29.4% and bone-specific alkaline phosphatase by 10.4% over 9 weeks in functionally impaired elderly. Resorption markers also increased, indicating acceleration of bone remodeling in both directions — formation and resorption — without evidence of pathologic uncoupling.

This work established one of the earliest demonstrations that an oral GH secretagogue can restore the somatotropic axis in the elderly with measurable effect on bone markers. Despite initial enthusiasm, subsequent studies (notably Nass 2008) showed that lean mass gain does not necessarily translate to functional strength improvement — a limitation that slowed clinical development of the compound for geriatric indications.