Shane E, Parisien M, Henderson J E, Dempster D W, Feldman F, Hardy M A, Tohme J F, Karaplis A C, Clemens T L
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
J Bone Miner Res. 1997 Sep;12(9):1502-11. doi: 10.1359/jbmr.1997.12.9.1502.
A patient with classic clinical and biochemical features of tumor-induced osteomalacia (hypophosphatemia, phosphaturia, and undetectable serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before and after resection of a benign extraskeletal chondroma from the plantar surface of the foot. Presurgical laboratory evaluation was notable for normal serum concentrations of calcium, intact parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and osteocalcin, increased serum alkaline phosphate activity, and frankly elevated urinary cyclic adenosine monophosphate (cAMP) and pyridinium cross-link excretion. Quantitative histomorphometry showed severe osteomalacia and deep erosions of the cancellous surface by active osteoclasts. After resection, serum 1,25(OH)2D normalized within 24 h, while renal tubular phosphorus reabsorption and serum phosphorus did not normalized until days 2 and 3, respectively; serum Ca declined slightly, and serum intact PTH, osteocalcin, and urinary pyridinium cross-link excretion increased dramatically. Urinary cAMP excretion declined immediately after resection and then began to increase concomitant with the increase in serum intact PTH. A second bone biopsy taken 3 months after resection demonstrated complete resolution of the osteomalacia, increased mineral apposition rate (1.09 mu/day), resorption surface (9.2%), mineralizing surface (71%), and bone formation rate (0.83 mm3/mm2/day), and marked decrease in cancellous bone volume (13.1%) and trabecular connectivity compared with first biopsy. Tumor extracts did not affect phosphate transport in renal epithelial cell lines or 1 alpha-hydroxylase activity in a myelomonocytic cell line. The patient's course suggests that the normal 1,25(OH)2D and phosphorus metabolism is due to a tumor product that may be acting via stimulation of adenylate activity. Increased bone resorption prior to surgical resection suggests that the tumor may also produce an osteoclast activator. The rise in resorption surface and pyridinium cross-link excretion, increase in serum osteocalcin and bone mineralization, normalization of osteoid width, and fall in cancellous bone volume after resection are consistent with healing of osteomalacia by rapid remodeling.
对一名患有肿瘤诱导性骨软化症典型临床和生化特征（低磷血症、磷尿症以及血清1,25 - 二羟维生素D [1,25(OH)2D]浓度检测不到）的患者，在切除足底的良性骨外软骨瘤之前和之后进行了研究。术前实验室评估结果显示，血清钙、完整甲状旁腺激素（PTH）、甲状旁腺激素相关蛋白（PTHrP）和骨钙素浓度正常，血清碱性磷酸酶活性升高，尿中环磷酸腺苷（cAMP）和吡啶交联物排泄明显升高。定量组织形态计量学显示存在严重骨软化症，活跃破骨细胞对松质骨表面造成深度侵蚀。切除术后，血清1,25(OH)2D在24小时内恢复正常，而肾小管磷重吸收和血清磷分别直到第2天和第3天才恢复正常；血清钙略有下降，血清完整PTH、骨钙素和尿吡啶交联物排泄显著增加。切除术后尿cAMP排泄立即下降，然后随着血清完整PTH的增加开始升高。切除术后3个月进行的第二次骨活检显示骨软化症完全消退，矿化沉积率（1.09μm/天）、吸收表面（9.2%）、矿化表面（71%）和骨形成率（0.83mm³/mm²/天）增加，与首次活检相比，松质骨体积（13.1%）和小梁连接性明显降低。肿瘤提取物不影响肾上皮细胞系中的磷酸盐转运或骨髓单核细胞系中的1α - 羟化酶活性。该患者的病程表明，正常的1,25(OH)2D和磷代谢归因于一种肿瘤产物，其可能通过刺激腺苷酸活性起作用。手术切除前骨吸收增加表明肿瘤可能还产生一种破骨细胞激活剂。切除术后吸收表面和吡啶交联物排泄增加、血清骨钙素和骨矿化增加、类骨质宽度恢复正常以及松质骨体积下降，与通过快速重塑治愈骨软化症一致。
