Theman Todd A, Collins Michael T, Dempster David W, Zhou Hua, Reynolds James C, Brahim Jaime S, Roschger Paul, Klaushofer Klaus, Winer Karen K
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
J Bone Miner Res. 2009 May;24(5):964-73. doi: 10.1359/jbmr.081233.
Autosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1-34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imaging (qBEI). Her data were compared with one age-, sex-, and length of hypoparathyroidism-matched control not on PTH and two sex-matched ADH controls before and after 1 yr of PTH. The patient's growth was normal. Hypercalciuria and hypermagnesuria persisted despite normal or subnormal serum calcium and magnesium levels. Nephrocalcinosis, without evidence of impaired renal function, developed by 19 yr of age. Cancellous bone volume was dramatically elevated in the patient and in ADH controls after 1 yr of PTH. BMD distribution (BMDD) by qBEI of the patient and ADH controls was strikingly shifted toward lower mineralization compared with the non-ADH control. Moreover, the ADH controls exhibited a further reduction in mineralization after 1 yr of PTH. These findings imply a role for CaR in bone matrix mineralization. There were no fractures or osteosarcoma. In conclusion, long-term PTH replacement in a child with ADH was not unsafe, increased bone mass without negatively impacting mineralization, and improved serum mineral control but did not prevent nephrocalcinosis. Additionally, this may be the first evidence of a role for CaR in human bone.
常染色体显性低钙血症（ADH）是一种由钙敏感受体（CaR）激活突变引起的遗传性甲状旁腺功能减退症。甲状旁腺激素（1-34）治疗可能优于传统疗法，但儿童禁用，其对骨骼的长期影响尚不清楚。该患者为一名20岁女性，自6岁2个月起持续接受甲状旁腺激素治疗ADH。进行骨活检以进行组织形态计量学和定量背散射电子成像（qBEI）。将她的数据与一名年龄、性别和甲状旁腺功能减退症病程匹配但未接受甲状旁腺激素治疗的对照以及两名性别匹配的ADH对照在接受甲状旁腺激素治疗1年前后的数据进行比较。患者生长正常。尽管血清钙和镁水平正常或低于正常，但高钙尿症和高镁尿症持续存在。19岁时出现肾钙质沉着症，但无肾功能受损证据。甲状旁腺激素治疗1年后，患者和ADH对照的松质骨体积显著升高。与非ADH对照相比，患者和ADH对照的qBEI骨密度分布（BMDD）明显向矿化程度较低的方向偏移。此外，ADH对照在接受甲状旁腺激素治疗1年后矿化程度进一步降低。这些发现表明CaR在骨基质矿化中起作用。未发生骨折或骨肉瘤。总之，对一名ADH儿童进行长期甲状旁腺激素替代治疗并非不安全，可增加骨量且对矿化无负面影响，并改善血清矿物质控制，但不能预防肾钙质沉着症。此外，这可能是CaR在人体骨骼中起作用的首个证据。
