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


OBJECTIVE
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 β 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 β 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.
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom. h.white@ukf.net
H D
HD
White
A M
AM
Ahmad
B H
BH
Durham
A A
AA
Joshi
W D
WD
Fraser
J P
JP
Vora
D000284:Administration, Oral; D019386:Alendronate / Q000627:therapeutic use*; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000097:blood; D002940:Circadian Rhythm / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D000242:Cyclic AMP / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000652:urine; D010455:Peptides; D010710:Phosphates / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; D011994:Recombinant Proteins; C052929:collagen type I trimeric cross-linked peptide; D019382:Human Growth Hormone; D000242:Cyclic AMP; D002117:Calcitriol; D019386:Alendronate