The histology of metabolic bone disease

Patients with metabolic bone disease are usually cared for by endocrinologists. Pathologists may examine specimens if fragility fractures occur or if a bone biopsy is required. Some metabolic bone diseases have distinctive histologic features such as tunneling resorption in hyperparathyroidism, wide osteoid seams in osteomalacia, and bone marrow edema in transient osteoporosis. The histologic changes must always be correlated with clinical and radiographic features.     

Aluminum accumulation in individuals with normal renal function

In individuals with normal renal function, oral aluminum may be absorbed, but the kidneys are able to excrete the load, and significant pathology is not seen. If aluminum is given parenterally, however, it can accumulate in tissues and lead to osteomalacia or aplastic bone lesions. Low calcitriol and PTH levels are often seen, and may contribute to the bone disease. These findings in individuals with normal renal function add to the growing body of evidence that aluminum is toxic to bone.     

Alendronate improves vitamin d-resistant osteopenia triggered by gastrectomy in patients with gastric cancer followed long term

Gastrectomy/gastric bypass has been used for patients with gastric cancer, and its application is now expanding to treating patients with morbid obesity, the prevalence of which is increasing worldwide. It is well known that gastrectomy leads to osteopenia, but the underlying pathophysiology and optimum treatments for this disorder have not been delineated. We followed 13 patients who showed progressive osteopenia (bone mineral density T-score <-2.4 SD) after gastrectomy/gastric bypass due to gastric cancer and who were resistant to long-term treatment (mean, 6 years) of active vitamin D3 and prospectively studied the effects of alendronate, a bisphosphonate, on osteopenia-related parameters for 2 years. Oral administration of alendronate in addition to vitamin D3 led to remarkable improvement within 2 years, not only in clinical symptoms, such as radial bone fractures and lumbar pain, but also in parameters for osteopenia, including decreased bone mineral density of the lumbar spine (P < 0.01), decreased concentrations of calcium (P < 0.05), increased urine levels of deoxypyridinoline (P < 0.01), increased serum levels of bone-specific alkaline phosphatase (P < 0.01), increased serum levels of osteocalcin (P < 0.01), and increased serum levels of intact parathyroid hormone (P < 0.05), although body weight did not alter. These results suggest that bisphosphonate may improve osteopenia after gastrectomy/gastric bypass.     

髌骨软化症中西医治疗进展

髌骨软化症是一种髌骨软骨退行性病变,西医治疗早中期主要提倡保守治疗,包括关节腔内注射玻璃酸钠、口服硫酸氨基葡萄糖、非甾体类抗炎药等;晚期建议手术治疗,均有一定效果及毒副作用.中医认为本病多因伤后气血不足,瘀血阻滞风寒湿邪侵袭,或因年老体弱,肝肾亏虚,气血亏虚,卫外不固,不能濡润关节,风寒湿邪乘虚而入而发病,治疗主要有中药内服、外敷、熏洗、针灸、推拿等法,急则治其标,缓则治其本,因人制宜,标本兼顾.中西医结合治疗可取长补短.     

实体肿瘤血液动力学的三维数值模拟

目的　数值研究实体肿瘤内外三维微血管网及间质内的血液动力学。方法　数值生成实体肿瘤内外三维微血管网，根据Poiseuille定律和Darcy定律分别计算微血管内压强及肿瘤组织间质压、组织液流速。结果　肿瘤外部微血管内压强迅速降低，肿瘤内部微血管压强变化很小，可视为常数；肿瘤组织间质压呈现‘内高且平，外低且陡’的分布，组织液流速与之相反。结论　本模型得到了较为有效的肿瘤内外三维血管网结构；血液动力学计算结果与生理实际基本吻合，为研究肿瘤内药物输运提供了可信的模型及方法。     

Maxillary tumour-induced osteomalacia

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, defective vitamin D metabolism, and osteomalacia. In the case reported here, maxillary TIO was not diagnosed for 6 years, although initial complaints were reported when the patient was 12 years old. Meanwhile she suffered from profound growth limitation, pain, weakness, and spontaneous multiple bone fractures, culminating in complete loss of ambulatory ability and severe limitation in daily activities. At age 18 years, she finally received an accurate diagnosis and definitive treatment was administered. She underwent a partial maxillectomy with complete removal of the tumour, resulting in a full cure. Shortly afterwards the patient regained the ability to walk, no longer needing the wheelchair to which she had been confined. This definitive diagnosis was based on three modalities: (1) fibroblast growth factor 23 analysis (high levels of the secreted hormone were found on the left side of the maxilla in the facial vein and pterygoid plexus, pinpointing the tumour location), (2) octreotide scan, and (3) ⁶⁸Ga-DOTA-NOC-PET/CT. TIO removal via partial maxillectomy led to a complete reversal of this patient’s health condition, restoring her ability to walk and function. The importance of prompt employment of these diagnostic modalities and the high level of clinical suspicion required in such cases are clear.     

Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR)

Calcimimetics, which activate the extracellular calcium (Ca_o²⁺)-sensing receptor in the parathyroid and other tissues participating in Ca_o²⁺ homeostasis, were the first described allosteric activators of a G-protein-coupled receptor. Cinacalcet, the only calcimimetic currently approved for human use, is used clinically for treating secondary hyperparathyroidism (e.g., overactivity of parathyroid glands) in patients being dialyzed for chronic kidney disease. By sensitizing the parathyroids to Ca_o²⁺, cinacalcet lowers the circulating parathyroid hormone (PTH) level. It also reduces serum calcium and phosphate, changes increasing the percentage of patients achieving the guidelines recommended by the National Kidney Foundation (NKF) for these minerals. Studies are underway addressing whether better adherence to these guidelines in patients receiving cinacalcet reduces cardiovascular disease and related mortality, which are both common is the dialysis population. The second approved use of cinacalcet is for treating hypercalcemia in patients with inoperable parathyroid carcinoma. In this setting, it provides the first medical therapy chronically lowering serum calcium concentration in this condition, albeit not to normal in most patients. Its effect on the long-term prognosis of these patients, if any, is presently unclear. “Off-label” administration of cinacalcet [i.e., not yet approved by the US Food and Drug Administration (FDA)] effectively lowers serum calcium and/or PTH in various other forms of hyperparathyroidism and increases serum phosphate in renal phosphate-wasting syndromes by reducing PTH-induced phosphaturia. In the future, the drug could conceivably be utilized to modulate the activity of the CaSR in other tissues (i.e., kidney, colon) in therapeutically desirable ways.