Orthopedic Clinic König-Ludwig-Haus, Julius-Maximilians-Universität Würzburg, Brettreichstr. 11, 97070, Würzburg, Germany.
Alexion Pharmaceuticals, Inc., Boston, MA, USA.
Osteoporos Int. 2021 Dec;32(12):2505-2513. doi: 10.1007/s00198-021-06025-y. Epub 2021 Jul 2.
There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone.
Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP.
ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment.
Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment.
Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care.
目前对于阿法特司治疗对成人生长激素缺乏性矮小症患者的骨代谢和骨转换的影响知之甚少。本研究表明，接受阿法特司治疗的成人生长激素缺乏性矮小症患者的骨代谢和矿物质代谢生化标志物发生了显著变化，这可能反映了以前骨软化骨的重塑增强。
由于组织非特异性碱性磷酸酶（TNSALP）缺乏导致的生长激素缺乏性矮小症（HPP）可导致骨矿化和骨转换受损。尽管 HPP 可以用酶替代疗法阿法特司进行治疗，但关于阿法特司治疗如何影响成人生长激素缺乏性矮小症患者的矿物质代谢和骨转换的数据有限。
在一项名为 EmPATHY 的单中心、观察性研究中，收集了接受阿法特司治疗的儿科起病 HPP 成年患者（≥18 岁）的碱性磷酸酶底物、骨转换和矿物质代谢标志物以及骨密度（BMD）数据，这些数据是在常规临床护理期间收集的，并在基线至 24 个月的治疗期间进行了分析。
21 名患者的数据显示，在接受阿法特司治疗的 24 个月内，碱性磷酸酶活性显著升高，尿磷乙醇胺（PEA）/肌酐（Cr）比值降低。甲状旁腺激素 1-84（PTH）、骨钙素和Ⅰ型前胶原 N 端肽（P1NP）水平在 3 个月和 6 个月时出现显著的一过性升高，TRAP5b 水平在 3 个月时升高，而Ⅰ型胶原 N 端肽（NTX）水平在 24 个月时降低。腰椎 BMD T 评分在治疗期间持续增加。
阿法特司治疗后骨转换和矿物质代谢标志物的显著变化表明，治疗介导的矿化可能使以前未矿化的表面能够进行重塑和骨转换。尿 PEA/Cr 比值可能是监测常规护理中治疗的有用参数。
