PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism.

Hypoparathyroidism is associated with abnormal structural and dynamic skeletal properties. We hypothesized that parathyroid hormone(1-84) [PTH(1-84)] treatment would restore skeletal properties toward normal in hypoparathyroidism. Sixty-four subjects with hypoparathyroidism were treated with PTH(1-84) for 2 years. All subjects underwent histomorphometric assessment with percutaneous iliac crest bone biopsies. Biopsies were performed at baseline and at 1 or 2 years. Another group of subjects had a single biopsy at 3 months, having received tetracycline before beginning PTH(1-84) and prior to the biopsy (quadruple-label protocol). Measurement of biochemical bone turnover markers was performed. Structural changes after PTH(1-84) included reduced trabecular width (144 ± 34 µm to 128 ± 34 µm, p = 0.03) and increases in trabecular number (1.74 ± 0.34/mm to 2.07 ± 0.50/mm, p = 0.02) at 2 years. Cortical porosity increased at 2 years (7.4% ± 3.2% to 9.2% ± 2.4%, p = 0.03). Histomorphometrically measured dynamic parameters, including mineralizing surface, increased significantly at 3 months, peaking at 1 year (0.7% ± 0.6% to 7.1% ± 6.0%, p = 0.001) and persisting at 2 years. Biochemical measurements of bone turnover increased significantly, peaking at 5 to 9 months of therapy and persisting for 24 months. It is concluded that PTH(1-84) treatment of hypoparathyroidism is associated with increases in histomorphometric and biochemical indices of skeletal dynamics. Structural changes are consistent with an increased remodeling rate in both trabecular and cortical compartments with tunneling resorption in the former. These changes suggest that PTH(1-84) improves abnormal skeletal properties in hypoparathyroidism and restores bone metabolism toward normal euparathyroid levels.

Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population.

More than 20 mutations of the Sequestosome 1 (SQSTM1) gene have been reported in patients of European descent affected by Paget's disease of bone (PDB). In this investigation, a systematic screening for SQSTM1 mutations was conducted in consecutively evaluated unrelated patients with phenotypical PDB living in the New York City area (NY, United States). Seventy unrelated PDB patients with a multiethnic background, mostly of Jewish, Italian American, and Western European ancestries, were recruited. Sequencing of exons 7 and 8 was performed on DNA samples isolated from peripheral blood. Seven patients (10%) had SQSTM1 mutations, of which three had a family history of PDB. Four patients carried the C1215T (P392L) mutation, and three patients carried novel SQSTM1 missense mutations: T1085A (S349T), C1209T (A390V), and T1290A (L417Q) mutations. All PDB patients with SQSTM1 mutations had polyostotic involvement, and the mean number of affected bones was significantly higher in pagetic patient carriers of a SQSTM1 mutation when compared to non-mutated PDB patients (4.0 vs. 2.0, respectively; P = 0.003). Haplotype analysis in patient carriers of the P392L mutation revealed that all P392L mutations were carried by haplotype 2. The SQSTM1 mutation rate in unrelated American patients described in the present study was similar to that reported in European populations.

A 10-year single-institutional study of the biofragmentable anastomosis ring.

BACKGROUND: The biofragmentable anastomosis ring (BAR) was introduced by Hardy in 1985 as a simple alternative to sutured or stapled intestinal anastomosis. METHODS: The aim of this study was to analyze complications related to the use of the BAR in elective intraperitoneal intestinal anastomosis to identify technical aspects important in the safe use of the device. The BAR was used by a single surgeon over a 10-year period. Three hundred fifty sequential intraperitoneal anastomoses were performed in 346 patients. There were 12 enteroenteric, 2 gastrojejunal, 199 enterocolic, and 137 colocolic anastomoses. RESULTS: There was 1 suture line recurrent carcinoma but no strictures. There were 11 complications that appeared related to construction of the anastomosis, 2 of them resulting in death. The 2 patients who died both had cirrhosis with ascites. Eight patients required re-exploration for suspected anastomotic complications. Six of them recovered and were discharged. CONCLUSION: The BAR appears to be a safe alternative to sutured or stapled bowel anastomosis provided certain precautions are taken in its use.