Introduction: Adult Growth Hormone Deficiency (AGHD) is associated with osteoporosis. Underlying mechanisms involved in the pathogenesis include reduced target-organ sensitivity to the effect of PTH. Growth Hormone Replacement (GHR) in AGHD leads to increased PTH target-organ sensitivity and consequently increased bone turnover and bone mineral density (BMD).
Aims: We determined the effect of alendronate, given in addition to GHR, on PTH target-organ sensitivity, bone turnover and BMD.
Methods: 13 AGHD patients with low BMD (defined as T-score <−1.0) were consented to the study. All patients were receiving standard pituitary hormone replacement, including GHR, for >2years prior to recruitment. Patients were hospitalised for 24 h where ½-hourly blood samples were taken for PTH, nephrogenous cyclic AMP (NcAMP, marker of renal PTH activity), calcium (adjusted for albumin, ACa), PINP (bone formation marker) and βCTX (bone resorption marker). Patients were randomised to receive GHR alone or GHR+alendronate 70 mg/week. The study visit and BMD measurement was repeated after 12 months. Results are expressed as mean±S.E.M.
Results: Patients receiving alendronate+GHR, had a significant increase in 24 h-mean PTH (3.51±0.16 pmol/L versus 4.03±pmol/L), with simultaneous decreases in NcAMP (26.6±3.1 nmol/L GFR versus 14.3±2.8 nmol/LGFR), ACa (2.34±0.004 mmol/L versus 2.23±0.003 mmol/L), PINP (58.6±8.8 mcg/L versus 24.0±8.4 mcg/L) and βCTX (0.49±0.05 mg/ml versus 0.12±0.04 mg/ml); indicating a reduction in PTH target-organ sensitivity (all P<0.001). In patients continuing GHR alone, the measured biochemical markers did not change significantly. Increase in lumbar spine BMD was significantly greater in the alendronate+GHR group (3.9±1.3% versus 1.6±1.3%, P=0.02).
Conclusions: The greater increase in BMD seen with alendronate+GHR compared with GHR alone was due to reduced bone resorption. Alendronate appears to attenuate mechanisms important for the anabolic effect of GHR on bone. Long-term administration of alendronate may blunt continued increase in BMD observed with GHR alone. The optimal length of bisphosphonate therapy in AGHD patients receiving GHR is unknown.