Vitamin D deficiency is a highly prevalent condition. Low vitamin D levels have long been associated with bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults. However, it has become apparent in recent years that adequate vitamin D levels are also important for optimal functioning of many organs and tissues throughout the body, including the cardiovascular system. Evolving data indicate that vitamin D deficiency is associated with an increased risk of cardiovascular disease (CVD). Studies have shown that low vitamin D levels are associated with hypertension, diabetes, metabolic syndrome, left ventricular hypertrophy, and chronic vascular inflammation, all of which are risk factors for CVD. This paper reviews the definition and pathophysiology of vitamin D deficiency, clinical evidence linking vitamin D and CVD risk, diabetes and its complications, and metabolic syndrome.

Osteomalacia is defined as a defect in mineralization of the bone matrix. We describe the case of a patient with chronic hepatitis B infection in whom treatment with adefovir induced renal phosphate loss with intense and sustained hypophosphatemia which derived in symptomatic osteomalacia.

Phosphate is widely distributed in the body and an adequate balance is required for maintaining essential cellular and organ functions. Dysregulation of phosphate balance, either in the form of hypophosphatemia or hyperphosphatemia can induce disorders ranging from rickets/osteomalacia to cardiovascular calcification. A physiologic phosphate balance is delicately maintained by multiorgan cross-talks among the intestine, kidney, and bone. Sodium-dependent phosphate (Na/Pi) cotransporters present in the intestine and kidney play a major role in phosphate absorption and reabsorption, according to the body's demand. Some of the calcium regulating factors, including parathyroid hormone and vitamin D can influence the activities of Na/Pi cotransporters, and thereby can affect phosphate balance. In addition, molecular analysis of the unexplained hypophosphatemic diseases, including autosomal-dominant hypophosphatemic rickets and tumor-induced osteomalacia has led to the identification of fibroblast growth factor 23 (FGF23). Subsequent studies have documented that bone-derived FGF23 and kidney-derived klotho can form an endocrine network to control urinary phosphate excretion. Studies have also documented negative effect of FGF23/klotho system on vitamin D metabolism and Na/Pi cotransporter activities. This article will summarize how the FGF23/klotho system might influence systemic phosphate metabolism, and consequences of its abnormal regulation will be briefly described.

The common denominator for all types of rickets is hypophosphatemia, leading to inadequate supply of the mineral to the growing bone. Hypophosphatemia can result from insufficient uptake of the mineral from the gut or its disproportionate losses in the kidney, the latter being caused by either tubular abnormalities per se or the effect on the tubule of circulating factors like fibroblast growth factor-23 and parathyroid hormone (PTH). High serum levels of the latter result in most cases from abnormalities in vitamin D metabolism which lead to decreased calcium absorption in the gut and hypocalcemia, triggering PTH secretion. Rickets is a disorder of the growth plate and hence pediatric by definition. However, it is important to recognize that the effect of hypophosphatemia on other parts of the skeleton results in osteomalacia in both children and adults. This review addresses the etiology, pathophysiologic mechanisms, clinical manifestations and treatment of entities associated with hypophosphatemic rickets due to perturbations in renal tubular function.

Oncogenic osteomalacia is a rare paraneoplastic syndrome induced by mesenchymal tumors. Just over 100 cases have been reported for this rare disorder, and only seven instances were caused by phosphaturic mesenchymal tumors of the spine. The authors present an illustrative case of a 61-year-old woman with oncogenic osteomalacia induced by a tumor of the spine, and review the literature describing the clinical presentation, surgical treatment, and follow-up of this syndrome.

BACKGROUND:

Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status.

OBJECTIVE:

We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity.

DESIGN:

In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated.

RESULTS:

At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL.

CONCLUSIONS:

Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297.

We studied the effect of metal mixture (MM), comprising As, Cd, and Pb, in developing female rat skeleton from gestation day 5 until postnatal day 60 (P-60). MM resulted in synergistic inhibition in viability and differentiation of osteoblasts in vitro, likely induced by reactive oxygen species. MM, administered at their most frequently occurring concentrations present in the groundwater of India, i.e., As: 0.38 ppm, Pb: 0.22 ppm, and Cd: 0.098 ppm or 10× of the ratio to developing rats, exhibited a synergistic decrease in ex vivo mineralization of bone marrow stromal (osteoprogenitor) cells. MM group showed a dose-dependent attenuation in weight and axial lengths and shortening of tibias at P-60. Furthermore, the growth plate was shortened, which was associated with shorter proliferative and hypertrophic zones, decreased parathyroid hormone-related protein and Indian hedgehog expression in the chondrocytes, reduced primary and secondary spongiosa, and hypomineralized osteoids-a major characteristic of osteomalacia. In addition, compared with the control, MM-treated rats were clearly osteopenic based on bone mineral density, microarchitecture, biomechanical strength, and particularly the biochemical profile, that suggested high turnover bone loss. Finally, in comparison to the control, the fracture-healing ability of MM group was delayed and accompanied by inferior quality of the healed bone. Together, these data demonstrated that the mixture of As, Cd, and Pb induced synergistic toxicity to developing skeleton, thereby diminishing modeling-directed bone accrual, inducing osteopenia and dampening fracture healing.

Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections and sarcoidosis. Clinical assessment should aim to distinguish proximal myopathy from other conditions that can present similarly, identify patients who need prompt attention, like those with cardiac, respiratory or pharyngeal muscle involvement, and determine underlying cause of myopathy. Initial evaluation should include simple tests, like creatine kinase, thyroid function and (25)OH vitamin D levels, but further evaluation including neurophysiological studies, muscle imaging and muscle biopsy should be considered for patients in whom no toxic, metabolic or endocrine cause is found, and in those with clinical features suggestive of inflammatory or hereditary myopathy. Additionally, screening for malignancy and testing for anti-Jo1 antibody is indicated for selected patients with IIM. Management depends on underlying cause, and includes measures, such as removal of offending agent, correction of endocrine or metabolic problem, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation and genetic counselling for muscular dystrophies.

WHAT IS KNOWN AND

OBJECTIVE:

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature.

CASE SUMMARY:

A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. WHAT IS NEW AND

CONCLUSION:

Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication.

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In Senegal, number of dialysis patients is growing but few data are available about their bone disorders.To describe patterns of CKD-MBD in Senegalese dialysis patients.We performed a cross-sectional study including patients from three dialysis centres in Senegal. Diagnosis of different types of CKD-MBD relied on clinical, biological and radiological data collected from medical records in dialysis.We included 118 patients and 79 of them presented CKD-BMD (prevalence of was 66.9 %). Mean age of CKD-MBD patients was 47.8 ± 15.7 years (16-81 years) and sex-ratio (Male/Female) was 1.15. Secondary hyperparathyroidism was the most frequent disorder (57 patients) followed by adynamic bone disease (21 patients) and osteomalacia (1 patients). The main clinical manifestations were bone pain (17.5% of cases), pruritus (36.8% of cases) and pathological fractures (2.5% of cases). Bone biopsy was not available. Valvular and peripheral vascular calcification were present in 24.5% and 21.2% of patients respectively. Management of CKD-MBD included optimization of dialysis, calcium bicarbonate, sevelamer, vitamin D analogues and calcimimetics. The NKF/DOQI recommended levels of serum calcium, phosphate and parathormone PTH were not achieved in one third of patients. Six patients presented major cardiovascular events during their dialysis period.CKD-MBD are frequent in Senegalese hemodialysis patients and they are dominated by high turn-over disease. Clinical and biological manifestations are unspecific and accurate diagnoses are often difficult in absence of histomorphometry. Treatment is suboptimal for many patients in a context of limited resources.