Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: A randomized controlled trial

We conducted a randomized controlled trial in osteoporotic adult GH-deficie nt (GHD) patients to assess whether additional treatment with a bisphosphon ate would further favorably influence parameters of bone turnover and bone mineral density measurements (BMD). All patients were receiving stable reco mbinant human (rhGH) replacement therapy for 4 yr at the start of the study . Eighteen GHD patients with osteoporosis were randomized to continue their rhGH maintenance dose or to receive combination therapy with rhGH and alen dronate for 12 months. All patients were calcium and vitamin replete, and t here were no changes in calcium, vitamin D, or hormone replacement therapy for the duration of the study. At baseline there were no significant differ ences between the alendronate and the control group in parameters of bone t urnover, BMD, or prevalence of vertebral fractures. Childhood-onset and adu lt-onset GHD were equally distributed between the groups, with no statistic al differences in age and gender or other parameters between groups. Mean s erum osteocalcin, serum bone-specific alkaline phosphatase, and urinary N-t elopeptide/creatinine ratio were within the normal range at the start of th e study. In the alendronate group all measured parameters of bone turnover, i.e. bone-specific alkaline phosphatase, osteocalcin, and urinary N-telope ptide/creatinine ratio, significantly decreased after 6 months, with no fur ther decrease thereafter. No changes were observed in the control group. In the alendronate-treated patients serum bone-specific alkaline phosphatase decreased from 10.9 +/- 0.9 to 6.8 +/- 0.7 mug/L at 6 months (P < 0.001), s erum osteocalcin decreased from 3.9 +/- 0.4 to 1.7 +/- 0.3 mug/L (P < 0.001 ), and the urinary N telopeptideicreatinine ratio decreased from 27.3 +/- 7 .0 to 6.4 +/- 0.8 nmol/mmol (P = 0.01). In this group, lumbar spine BMD sig nificantly increased from baseline by 3.4% at 6 months (P = 0.001) and by 4 .4% at 12 months (P < 0.001) of treatment, with no further significant incr ease between 6 and 12 months (P = 0.217). No changes in lumbar spine BMD we re observed in the control group. There were no significant changes in femo ral neck BMD in either group for the duration of the study. No incident ver tebral or peripheral fractures were documented in either group at the end o f the study. In summary, this is the first report indicating that treatment with alendro nate was able to significantly increase BMD at the lumbar spine in GHD pati ents with osteoporosis receiving stable rhGH replacement for 4 yr. This inc rease was significantly greater in alendronate-treated patients than in pat ients maintained on rhGH. The increase in lumbar spine BMD in the alendrona te-treated patients was associated with a decrease in the measured markers of bone turnover, whereas these markers did not change further in the patie nts maintained on rhGH. This controlled study suggests that additional trea tment with alendronate in GHD patients with osteoporosis receiving stable r hGH replacement therapy is effective in increasing BMD at the lumbar spine. Further investigation is required to assess whether rhGH replacement alone or combined treatment with rhGH and alendronate is able to reduce the incr eased fracture risk associated with GHD.