The calcium‐sensing receptor and 25‐hydroxyvitamin D–1α‐hydroxylase interact to modulate skeletal growth and bone turnover

We examined parathyroid and skeletal function in 3‐month‐old mice expressing the null mutation for 25‐hydroxyvitamin D–1α‐hydroxylase [1α(OH)ase^?/?] and in mice expressing the null mutation for both the 1α(OH)ase and the calcium‐sensing receptor [Casr^?/?1α(OH)ase^?/?] genes. On a normal diet, all mice were hypocalcemic, with markedly increased parathyroid hormone (PTH), increased trabecular bone volume, increased osteoblast activity, poorly mineralized bone, enlarged and distorted cartilaginous growth plates, and marked growth retardation, especially in the compound mutants. Osteoclast numbers were reduced in the Casr^?/?1α(OH)ase^?/? mice. On a high‐lactose, high‐calcium, high‐phosphorus “rescue” diet, serum calcium and PTH were normal in the 1α(OH)ase^?/? mice but increased in the Casr^?/?1α(OH)ase^?/? mice with reduced serum phosphorus. Growth plate architecture and mineralization were improved in both mutants, but linear growth of the double mutants remained abnormal. Mineralization of bone improved in all mice, but osteoblast activity and trabecular bone volume remained elevated in the Casr^?/?1α(OH)ase^?/? mice. These studies support a role for calcium‐stimulated maturation of the cartilaginous growth plate and mineralization of the growth plate and bone and calcium‐stimulated CaSR‐mediated effects on bone resorption. PTH‐mediated bone resorption may require calcium‐stimulated CaSR‐mediated enhancement of osteoclastic activity. © 2010 American Society for Bone and Mineral Research. © 2010 American Society for Bone and Mineral Research     

Levels and dynamic changes of serum fibroblast growth factor 23 in hypophosphatemic rickets/osteomalacia

Background Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast growth factor 23 （FGF-23） in the regulation of phosphate homeostasis, we measured the circulating concentrations of this growth factor in healthy individuals and in patients with hypophosphatemic rickets/osteomalacia. Methods Nineteen patients with hypophosphatemic rickets/osteomalacia were included in hypophosphatemic group （HP, 12 female and 7 male, mean age was 30 years）, and 19 healthy age-matched individuals served as the control group. Full length FGF-23 fragments were measured by two-site enzyme-linked immunosorbent assay.Results Mean FGF-23 concentrations were significantly higher in the HP group （（87.4±43.6） pg/ml） compared with the control group （（19.2±6.16） pg/ml; P 〈0.001）. In 1 patient with tumour-induced osteomalacia, serum FGF-23 concentrations were 84.1 pg/ml; these concentrations were normalized 2 hours after a hemangiopericytoma resection （7.8 pg/ml）. Subsequently, serum 1,25（OH）2 vitamin D3 concentrations significantly increased from 21.3 pg/ml to 89.3 pg/ml, and serum phosphorus levels were normalized. Conclusions Serum FGF-23 concentrations were markedly elevated in patients with hypophosphatemic rickets. FGF-23 plays an important role in the pathogenesis of hypophosphatemic rickets/osteomalacia.     

缝匠肌前移治疗髌股关节痛

目的　探讨髌股关节痛、髌骨软骨软化症的治疗方法。方法　游离缝匠肌下１／３ 段， 其止点不切断，前移，建立一动力性髌韧带，加强股内侧肌肌力，产生髌骨向内可变拉应力，使Ｑ 角变小，恢复髌股关节面的正常生物力学应力分布，恢复髌骨在股骨滑车和髁间沟内的矢状面、冠状面的正常滑动。结果　随访７ 例８ 膝，随访时间３ 年６ 个月～６ 年。临床症状消失，关节伸屈活动正常。结论　该方法适用于髌股韧带外侧紧张、内侧松驰、Ｑ 角大于正常角所引起的髌骨软骨软化症、髌骨半脱位、复发性髌骨脱位的治疗。     

Secondary hyperparathyroidism as a palpable intrathyroid parathyroid gland in a patient with hypophosphatemic osteomalacia

Secondary hyperparathyroidism is sometimes seen in patients with hypophosphatemic osteomalacia after long-term oral phosphate therapy. Parathyroidectomy is sometimes needed for the correction of hypercalcemia in these patients, and is rarely performed in patients without hypercalcemia. A 46-year-old female patient had hypophosphatemic osteomalacia with unknown cause and secondary hyperparathyroidism. A palpable neck mass developed after long-term oral phosphate therapy. An intrathyroid parathyroid gland was confirmed through partial thyroidectomy and parathyroidectomy. Renal phosphate wasting decreased strongly, and serum parathyroid hormone was in the normal range after the operation. A correction of secondary hyperparathyroidism may partially overcome hyperphosphaturia in some patients with hypophosphatemic rickets.     

Hypovitaminosis D-induced pain

Vitamin D deficiency is a problem of considerable magnitude that has reemerged as a major public health issue in the United States and several other developed countries. Vitamin D plays a crucial role in calcium homeostasis in the body. Hypovitaminosis D leads to osteomalacia and increased risk of fractures, especially in the elderly. Preliminary research suggests that vitamin D can prevent certain types of cancer and autoimmune diseases. A recent large study has shown the association between severe hypovitaminosis D and persistent, non-specific musculoskeletal pain, further suggesting that patients with no apparent cause of pain should be assessed and possibly treated for vitamin D deficiency.     

Vitamin D deficiency and aging: implications for general health and osteoporosis

Vitamin D deficiency is extremely prevalent in the elderly. Most often the first symptoms are caused by myopathy with muscle pain, fatigue, muscular weakness and gait disturbances. More severe deficiency causes osteomalacia with deep bone pain, reduced mineralization of bone matrix and low energy fractures. Recent data also suggest that hypovitaminosis D increases the risk of cancer of the prostate, colon and breast. Thus, hypovitaminosis D is associated with many diseases associated with aging. In order to diagnose hypovitaminosis D, the assessment of serum levels of 25-hydroxy vitamin D is mandatory. Screening based on other markers like alkaline phosphatase and parathyroid hormone (PTH) will be incomplete. The treatment of hypovitaminosis D is simple with administration of combined calcium (1 g) and vitamin D supplements(calciferol, at least 800 IU). Severe cases may demand initial parenteral administration of vitamin D (repeated injections of 300,000 IU 2–3 times with monthly intervals). More potent analogues are rarely needed. One should aim at achieving S-25(OH)D values in the range 50–100 nmol/l. This revised version was published online in July 2006 with corrections to the Cover Date.     

5p;12q translocation with manifestations of cri du chat syndrome and Marfanoid arachnodactyly

A 12-year-old boy with a history of a mewing cry after birth, severe mental retardation, Marfanoid arachnodactyly, general osteomalacia and multiple bone fractures was found to have a de novo 5p;12q chromosomal translocation. The karyotype is 46,XY,t(5;12)(12qter----12q24.1::5p15----cen----5qt er; 12pter----cen----12q24.1). The karyotypes of other examined family members are normal. The manifestations of cri du chat syndrome are explained by the loss of a small segment of 5p15 which is responsible for the major stigmata of the syndrome, and the abnormalities of the osseous system may be the results of untreated vitamin D resistant rickets.     

甲状腺功能亢进症合并骨软化1例并文献复习

甲状腺功能亢进(简称甲亢)是导致碱性磷酸酶升高的原因之一,在甲亢的治疗过程中,如碱性磷酸酶进行性升高,伴骨痛,不能排除骨软化的可能性,值得引起注意。随着对代谢病骨病研究的深入,骨软化患者逐渐增多,病因包括维生素D摄入不足、维生素D吸收和代谢障碍、肾脏疾病(肾病综合征、慢性肾衰、肾小管酸中毒、范可尼综合征等),以及遗传性和肿瘤性低磷性骨软化,其他如重金属中毒、高氟摄入、某些药物等。然而,甲状腺功能亢进症患者出现骨质疏松多见,出现骨软化者较少见,罕有报道,容易漏诊和误诊。本文报道l例甲状腺功能亢进患者口服赛治(甲巯咪唑)后碱性磷酸酶进行性升高,伴全身骨痛,应用骨化三醇后碱性磷酸酶逐渐下降和骨痛消失。为此,甲亢治疗期间,结合国外文献报告,考虑骨软化可能性较大,密切观察患者碱性磷酸酶变化,给予积极对症治疗后,骨软化症状明显缓解。因此,应重视碱性磷酸酶的变化及临床特点,以明确是否合并骨软化并予尽早处理。     

Calcium phosphate cement for augmentation did not improve results after internal fixation of displaced femoral neck fractures: A randomized study of 118 patients

Background?We wanted to evaluate whether augmentation with calcium phosphate cement can improve clinical and functional outcome following internal fixation of displaced femoral neck fractures.

Patients?118 patients aged 60–98 years (95 women) were included. All patients were physically active and ambulatory before the fracture. Patients were randomized to treatment with closed reduction and fixation with two cannulated screws alone (controls: 60 patients) or screws combined with injection of calcium phosphate for augmentation around the screw threads and at the fracture site (augmented: 58 patients). All patients were allowed free weight bearing. Clinical and radiographic examinations were done by a physiotherapist directly after surgery, at 1 and 6 weeks, and at 6, 12 and 24 months.

Results?24 patients, 14 augmented and 10 controls, died during the follow-up. There was 1 deep infection (augmented). Another 34 patients were reoperated with a total arthroplasty (20 in the augmented group and 14 controls) due to loss of reduction, nonunion or avascular necrosis (p = 0.1). There was no difference in pain or muscle strength between groups. Some activities of daily living (ADLs) were slightly better in the augmented patients during the first weeks, while there were no differences between groups later on.

Interpretation?Due to a trend towards more reoperations in the augmented group, and only a temporary clinical improvement during the early rehabilitation, augmentation as we used it cannot be recommended.