Adult Growth Hormone Deficiency (AGHD) is associated with reduced bone mineral density (BMD) and bone turnover. Abnormalities in PTH circadian rhythmicity, including blunted nocturnal rise in PTH concentration have been reported in AGHD and may underlie the pathogenesis of osteoporosis. Serum phosphate is an important regulator of PTH, with changes in phosphate concentration preceding fluctuations in PTH. We examined the effect of oral phosphate therapy on PTH circadian rhythmicity, bone turnover and BMD.
17 AGHD patients were consented to the study. Patients were randomised to receive either growth hormone replacement (GHR) alone or GHR plus 1 g phosphate-sandoz administered at 2200 h. Patients were admitted to hospital for 24 h before and 12 months after initiation of therapy where ½-hourly blood samples were collected for PTH, phosphate, CTX (marker of bone resorption) and PINP (marker of bone formation). BMD was measured at baseline and after 12 months. The local ethics committee approved the study. Results are expressed as mean±SEM.
Each patient and both groups had significant PTH and phosphate circadian rhythms at both visits (P<0.001). There was no significant difference in any measured marker at baseline between the groups. The patients receiving oral phosphate therapy had significantly greater increases in mean nocturnal rise in PTH (21.4±1.8% versus 17.5±1.6%, P<0.001) and phosphate (15.4±1.2% versus 6.3±1.4%, p<0.001) at 12 months, compared with patients receiving GHR alone. The percentage increase in bone turnover markers and BMD was significantly higher in patients receiving phosphate (CTX 79.7±7.3% versus 56.4±6.9%; PINP 121.3±10.4% versus 93.4±8.9%; femoral BMD 6.8±0.9% versus 1.9±0.8%; lumbar BMD 7.1±1.6% versus 1.8±1.2%, all P<0.001).
Oral phosphate therapy appears to potentiate the effect of GHR on bone turnover and BMD. Phosphate therapy administered at 2200 h results in a greater nocturnal rise in PTH concentration, which may be important for the stimulation of bone turnover and increase in BMD.
01 - 05 Apr 2006
European Society of Endocrinology