QUANTITATIVE BONE HISTOMORPHOMETRY IN HUMORAL HYPERCALCEMIA OF MALIGNANCY - UNCOUPLING OF BONE CELL-ACTIVITY
QUANTITATIVE BONE HISTOMORPHOMETRY IN HUMORAL HYPERCALCEMIA OF MALIGNANCY - UNCOUPLING OF BONE CELL-ACTIVITY
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DOI：
10.1210/jcem-55-2-219
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发表时间：
1982-01-01
影响因子：
5.8
通讯作者：
BARON, R
中科院分区：
文献类型：
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作者：
STEWART, AF;VIGNERY, A;BARON, R
恶性体液高钙血症是由肿瘤分泌的一种循环骨吸收因子引起的(S)。这种骨吸收因子的具体机制(S)。导致这种骨吸收的具体机制尚不清楚，也没有对活体HHM患者的骨活检进行定量组织形态计量学分析的全面研究报道。骨组织学和定量骨组织形态计量学从7名患者的骨活检中描述，这些患者的生化(肾源性cAMP排泄升高)和组织学(活检样本中无肿瘤)被定义为HHM。将这些活检与9例原发性甲状旁腺功能亢进症(HPT)患者的活检进行比较。与HPT患者相比，HHM患者表现为(平均值+-。SD)更大的破骨活性(破骨细胞表面，8.6.+-。6.1%比2.7.+-。1.5%；P<；0.001)和更常见的空陷窝(9.2+-)。4.0%比5.8.+-。3.0%；P<；0.01)，但成骨细胞表面明显减少(2.5±-)。3.1%对13.8.+-7.0%；P<；0.001)，类骨质表面(12.9±-)。11.9%对42.0.+-15.0%；P<；0.001)，类骨质体积(0.30±-)。0.3%对1.3%+-。1.0%；P<；0.01)。这些发现直接证实了体液介导的骨吸收的存在，并表明HHM患者骨骼中的破骨细胞和成骨细胞活动显著解偶联。这些发现与HPT患者形成鲜明对比，在HPT患者中，破骨细胞和成骨细胞活动紧密耦合，骨骼净钙损失最小。这种解偶联为HHM患者观察到明显的骨骼钙丢失提供了一种机制。
Humoral hypercalcemia of malignancy (HHM) results from elaboration by tumors of a circulating bone-resorbing factor(s). The specific mechanism responsible for this bone resorbing factor(s). The specific mechanism responsible for this bone resorption is poorly understood, and no comprehensive study employing quantitative histomorphometric analyses of bone biopsies obtained from living patients with HHM has been reported. Bone histology and quantitative bone histomorphometry are described in bone biopsies obtained from 7 patients defined biochemically (elevated nephrogenous cAMP excretion) and histologically (no tumor in biopsy sample) as having HHM. These biopsies are compared to biopsies from 9 patients with primary hyperparathyroidism (HPT). Compared to patients with HPT, those with HHM displayed (mean .+-. SD) greater osteoclastic activity (osteoclast surface, 8.6 .+-. 6.1% vs. 2.7 .+-. 1.5%; P < 0.001) and more frequent empty lacunae (9.2 .+-. 4.0% vs. 5.8 .+-. 3.0%; P < 0.01), but markedly reduced osteoblastic surface (2.5 .+-. 3.1% vs. 13.8 .+-. 7.0%; P < 0.001), osteoid surface (12.9 .+-. 11.9% vs. 42.0 .+-. 15.0%; P < 0.001), and osteoid volume (0.3 .+-. 0.3% vs. 1.3 .+-. 1.0%; P < 0.01). These findings directly confirm the presence of humorally mediated bone resorption and indicate a striking uncoupling of osteoclast and osteoblast activities in bone from patients with HHM. These findings are in sharp contrast to those in HPT patients, where osteoclast and osteoblast activities are tightly coupled, and net skeletal Ca loss is minimal. This uncoupling provides a mechanism for the marked skeletal Ca losses observed in patients with HHM.