Singer F, Siris E, Shane E, Dempster D, Lindsay R, Parisien M
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York.
J Bone Miner Res. 1994 May;9(5):733-8. doi: 10.1002/jbmr.5650090519.
We provide a 20 year follow-up of a family with three siblings affected by hereditary hyperphosphatasia (HH). An iliac crest bone biopsy was performed on one of the siblings following double-tetracycline labeling, with results reported quantitatively in a standard histomorphometric format. Biochemical parameters of disease activity were monitored in the patient before and after treatment with oral etidronate disodium, 20 mg/kg/day taken for 5 weeks. Biochemical evidence of intense disease activity continued 20 years after the initial diagnosis of HH in the sibling studied. His bone biopsy specimen also revealed extremely high bone turnover but low cancellous bone volume and osteoclasts unlike those found in Paget's disease. Treatment with etidronate disodium resulted in a temporary 40% reduction in serum alkaline phosphatase and 24 h urine hydroxyproline excretion, with reduction in serum osteocalcin from two times the upper limit of normal to a subnormal level. We conclude that disease activity in HH can continue unabated for two decades. Our bone biopsy finding of low cancellous bone volume, the consistent lack of pagetic-looking osteoclasts in our and other studies, plus the clinical features of HH (childhood onset and extremely diffuse disease with gross skeletal deformation) serve to distinguish HH from Paget's disease. Bisphosphonates may be of value in treating HH.
我们对一个有三名患遗传性高磷酸酶血症（HH）的兄弟姐妹的家庭进行了20年的随访。对其中一名兄弟姐妹进行了双四环素标记后的髂嵴骨活检，并以标准组织形态计量学格式定量报告结果。在用口服依替膦酸二钠（20mg/kg/天，服用5周）治疗前后，对该患者的疾病活动生化参数进行了监测。在对所研究的兄弟姐妹首次诊断HH后20年，仍有疾病活动剧烈的生化证据。他的骨活检标本还显示骨转换极高，但松质骨体积低，且破骨细胞与佩吉特病不同。依替膦酸二钠治疗使血清碱性磷酸酶和24小时尿羟脯氨酸排泄量暂时降低了40%，血清骨钙素从正常上限的两倍降至低于正常水平。我们得出结论，HH的疾病活动可以持续二十年而不减弱。我们骨活检发现松质骨体积低，我们的研究和其他研究中一直缺乏佩吉特样破骨细胞，再加上HH的临床特征（儿童期发病和伴有严重骨骼变形的极其弥漫性疾病）有助于将HH与佩吉特病区分开来。双膦酸盐可能对治疗HH有价值。
