Appelman-Dijkstra Natasha M, Claessen Kim M J A, Hamdy Neveen A T, Pereira Alberto M, Biermasz Nienke R
Department of Endocrinology and Metabolism, Center for Endocrine Tumors Leiden and, Leiden, The Netherlands; Center for Bone Quality Leiden, Leiden University Medical Center, Leiden, The Netherlands.
Clin Endocrinol (Oxf). 2014 Nov;81(5):727-35. doi: 10.1111/cen.12493. Epub 2014 Jun 5.
Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7 years of treatment. Data on longer follow-up are, however, scarce.
Two hundred and thirty-adult GHD patients (mean age 47·1 years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5 years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15 years of rhGH replacement. In addition, clinical fracture incidence was assessed.
Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10 years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1 year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000 py.
Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement.
成年人生长激素缺乏（GHD）可能与骨矿物质密度（BMD）降低、骨矿物质含量（BMC）减少以及骨折风险增加有关。重组人生长激素（rhGH）替代治疗在长达5至7年的治疗期间可使BMD逐渐增加。然而，关于更长随访期的数据却很稀少。
本研究纳入了230例成年GHD患者（平均年龄47.1岁，52.6%为女性），其中88%的患者为成年起病（AO）GHD，接受rhGH替代治疗≥5年。大多数患者存在多种垂体激素缺乏。在基线时以及rhGH替代治疗5年、10年和15年后，评估骨转换标志物、BMC、BMD以及腰椎和股骨颈的T值。此外，还评估了临床骨折发生率。
在rhGH替代治疗的前10年中，腰椎平均BMD、腰椎BMC和T值逐渐增加，此后保持稳定。rhGH补充治疗对男性的效果最为显著。在使用双膦酸盐的小部分患者中，长期使用双膦酸盐并未影响额外的有益效果。低基线BMD对BMD和BMC随时间的变化有积极影响，但1年时高GH剂量对BMD和BMC随时间的变化有负面影响。长期rhGH替代治疗期间的临床骨折发生率为20.1/1000人年。
成年GHD患者接受15年的rhGH替代治疗可使腰椎BMD值持续增加，尤其是在男性中，并且股骨颈BMD值趋于稳定。长期rhGH替代治疗期间临床骨折发生率未见增加。
