title: PTH(1-34) replacement therapy in a child with hypoparathyroidism caused by a sporadic calcium receptor mutation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Theman
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Brahim
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.forename: Karen K
authors.initials: KK
authors.lastname: Winer
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D002648:Child; D003720:Densitometry; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000652:urine; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012886:Skull / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing