Effect of oral phosphate and alendronate on bone mineral density when given as adjunctive therapy to growth hormone replacement in adult growth hormone deficiency.

Author(s): White HD, Ahmad AM, Durham BH, Joshi AA, Fraser WD, Vora JP

Affiliation(s): Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom. h.white@ukf.net

Publication date & source: 2011-03, J Clin Endocrinol Metab., 96(3):726-36. Epub 2011 Jan 20.

Publication type: Randomized Controlled Trial

BACKGROUND: Adult GH deficiency (AGHD) is associated with osteoporosis, which occurs as the result of reduced sensitivity of the bone and kidney to the effect of PTH. AIM: The aim of the study was to examine the effect of oral phosphate and alendronate therapy on PTH sensitivity, bone turnover, and bone mineral density (BMD) in AGHD patients. METHODS: Forty-four AGHD patients were hospitalized for 24 h, and half-hourly blood and 3-hourly urine samples were collected for PTH, nephrogenous cAMP (marker of renal PTH activity), procollagen type-I amino-terminal propeptide, and type-I collagen beta C-telopeptide. Patients were randomized to one of six groups: patients who were previously naive to GH were randomized to receive GH replacement (GHR) alone, GHR+alendronate, or GHR+phosphate-sandoz, whereas patients already receiving GHR were randomized to continue GHR alone, GHR+alendronate, or GHR+phosphate-sandoz. Study visits were repeated after 1, 3, 6, and 12 months in the previously GH-naive group and after 12 months in the previously GH-replaced group. BMD was measured at 0 and 12 months. RESULTS: Patients receiving GHR+phosphate had greater increases in nephrogenous cAMP and bone markers than patients receiving GHR alone (P < 0.01), and this was associated with greater increases in BMD (P < 0.01). In the GHR+alendronate groups, type-I collagen beta C-telopeptide decreased (P < 0.001), and BMD increases were greater than in those receiving GHR alone (P < 0.05). The greatest increases in BMD were seen in patients receiving GHR+phosphate. CONCLUSIONS: Phosphate and alendronate therapy given in combination with GHR confer advantage in terms of BMD increase. Phosphate appears to exert its effect by increasing PTH target-organ action, whereas alendronate acts primarily through reduction in bone resorption.