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Historically vitamin D deficiency had devastating consequences for children causing rickets resulting in severe bone deformities often leading to death. The mystery of the cause of rickets finally came to light when it was observed that cod liver oil and sunlight could prevent and cure rickets. The first vitamin D to be discovered was vitamin D 2 from ergosterol in ultraviolet irradiated yeast. Vitamin D 3 was discovered from UV exposure to the skin. Investigations revealed the two major functions of vitamin D were to increase intestinal calcium and phosphate absorption and mobilize calcium from the skeleton to maintain calcium and phosphorus homeostasis. Later studies demonstrated that vitamin D does not have an active role in bone mineralization. Vitamin D deficiency results in secondary hyperparathyroidism increasing bone resorption. As a result, this decreases bone mineral content and compromises the architectural integrity increasing risk for fracture. Vitamin D deficiency has also been shown to enhance aging of the bone causing cracks and enhancing bone fractures. Vitamin D deficiency also causes osteomalacia. Therefore, vitamin D sufficiency is extremely important to maximize bone health throughout life. It helps to prevent bone loss, but it cannot restore bone loss due to increased bone resorption that can occur under a variety of circumstances including menopause. The Endocrine Society Guidelines recommends for all ages that adequate vitamin D obtained from the sun, foods and supplements is necessary in order to maintain a circulating concentration of 25-hydroxyvitamin D of at least 30 ng/mL for maximum bone health., (Copyright © 2024. Published by Elsevier Inc.)

Background: Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary., Methods: We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades., Results: Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L)., Conclusions: Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change., Competing Interests: None of the authors have any financial conflicts of interest, but all authors have co-authored randomised controlled trials and systematic reviews of the efficacy of vitamin D supplements and co-authored articles concluding that there is no role for routine vitamin D supplementation in community dwelling individuals.

The study aimed to estimate vitamin D intake and plasma/serum 25-hydroxyvitamin D (25(OH)D) concentrations, investigate determinants of 25(OH)D concentrations and compare two 25(OH)D assays. We conducted two nationwide cross-sectional studies in Sweden with 206 school children aged 10-12 years and 1797 adults aged 18-80 years ( n 268 provided blood samples). A web-based dietary record was used to assess dietary intake. Plasma/serum 25(OH)D was analysed by liquid chromatography-mass spectrometry (LC-MS) and immunoassay in adults and LC-MS/MS in children. Most participants reported a vitamin D intake below the average requirement (AR), 16 % of children and 33 % of adults met the AR (7⋅5 μg). In adults, plasma 25(OH)D below 30 and 50 nmol/l were found in 1 and 18 % of participants during the summer period and in 9 and 40 % of participants during the winter period, respectively. In children, serum 25(OH)D below 30 and 50 nmol/l were found in 5 and 42 % of participants (samples collected March-May), respectively. Higher 25(OH)D concentrations were associated with the summer season, vacations in sunny locations (adults), and dietary intake of vitamin D and use of vitamin D supplements, while lower concentrations were associated with a higher BMI and an origin outside of Europe. Concentrations of 25(OH)D were lower using the immunoassay than with the LC-MS assay, but associations with dietary factors and seasonal variability were similar. In conclusion, vitamin D intake was lower than the AR, especially in children. The 25(OH)D concentrations were low in many participants, but few participants had a concentration below 30 nmol/l., (© The Author(s) 2020.)

The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D., (Copyright © 2019 Endocrine Society.)

Aluminium utensils are ubiquitous in Indian households and other developing countries. Concerns have recently been raised on the pathological effects of aluminium on the human body, due to its leaching from utensils with long-term use, which has been associated with certain clinical conditions such as anaemia, dementia and osteo-malacia. While some studies suggest that cooking in utensils or aluminium foils is safe, others suggest that it may lead to toxic levels of aluminium in the body. However, studies have shown that leaching of aluminium from cooking utensils depends on many factors such as pH, temperature and cooking medium. In healthy controls, 0.01 %-1 % of orally ingested aluminium is absorbed from the gastrointestinal tract and is eliminated by the kidney. Although the metal has a tendency to accumulate in tissues and may result in their dysfunction, the literature suggests that the apprehension is more apt in patients with chronic renal insufficiency. This article offers solutions to mitigate the risk of aluminium toxicity., Competing Interests: None

The consequences of vitamin D and dietary calcium deficiency have become a huge public health concern in the UK. The burden of disease from these deficiencies includes rickets, and hypocalcaemic seizures, dilated cardiomyopathy and mostly occult myopathy and osteomalacia. The increasing burden of the disease is intrinsically linked to ethnicity and the population demographic changes in the UK. Three facts have led to the resurfacing of the English disease: (1) the UK has no ultraviolet sunlight for at least 6 months of the year, (2) dark skin produces far less vitamin D than white skin per unit ultraviolet light exposure, and (3) non-European Union immigration over the last century. To date, the UK government demonstrates incomplete understanding of these three facts, and its failure to adjust its prevention programmes to changing demographics is endangering the health and life of UK residents with dark skin, of whom infants are the most vulnerable. Establishing accountability through the implementation of monitored antenatal and infantile supplementation programmes and mandatory food fortification is overdue., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Cadmium (Cd) and lead (Pb) are toxic elements that accumulate to the largest extent in bones. Rats were used to investigate whether tannic acid (TA; 0.5%, 1.0%, 1.5%. 2.0%, or 2.5%) would have a protective effect on the structure and properties of bones in the case of exposure to Cd and Pb (diet: 7 mg Cd/kg and 50 mg Pb/kg) for 6 weeks. The effects of administration of TA in Cd- and Pb-poisoned rats on bone characteristics and the morphology of articular and growth cartilages were determined. All the rats administered Cd and Pb had an enhanced Cd and Pb concentration in blood plasma and bone and reduced bone Ca content irrespective of the TA administration. Cd and Pb alone reduced the mechanical endurance and histomorphometric parameters of trabecular bone and the thickness of the growth plate and articular cartilage. Tannic acid improved cancellous bone parameters in the rat exposed to Cd and Pb. A diet rich in TA improved articular cartilage constituents in heavy metal-poisoned rats. These results suggest that alimentary TA supplementation can counteract in a dose-dependent manner some of the destructive changes evoked by Cd and Pb possibly by reducing the exposure.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome often associated with fibroblast growth factor 23 (FGF23)-producing tumors such as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) affecting the bone and soft tissue. We experienced a patient with progressive bone and muscle pain due to FGF23-related TIO. Venous sampling had strongly suggested the anterior skull base as a source of FGF23, which led to the discovery of a small tumor in the ethmoid sinus extending intracranially. Radical surgical resection confirmed the histological diagnosis of PMTMCT with FGF23 immunopositivity and achieved durable tumor control with complete resolution of symptoms. We serially measured serum FGF23 level before, during and after surgery and analyzed the data to determine the half-life of FGF23. Serum FGF23 level sharply declined as early as 20 minutes after en bloc tumor resection and completely normalized after surgery. The half-life of FGF23 was calculated to be approximately 18.5 minutes using single phase exponential decay model as well as semilog transformation formula. Serial measurements of serum FGF23 level can potentially declare "complete" resection of a FGF23-producing tumor and total cure of TIO; in this regard, development of its intraoperative measurement would be helpful in the management of this endocrine tumor.

Purpose of Review: Nutritional rickets and osteomalacia are common in dark-skinned and migrant populations. Their global incidence is rising due to changing population demographics, failing prevention policies and missing implementation strategies. The calcium deprivation spectrum has hypocalcaemic (seizures, tetany and dilated cardiomyopathy) and late hypophosphataemic (rickets, osteomalacia and muscle weakness) complications. This article reviews sustainable prevention strategies and identifies areas for future research., Recent Findings: The global rickets consensus recognises the equal contribution of vitamin D and dietary calcium in the causation of calcium deprivation and provides a three stage categorisation for sufficiency, insufficiency and deficiency. For rickets prevention, 400 IU daily is recommended for all infants from birth and 600 IU in pregnancy, alongside monitoring in antenatal and child health surveillance programmes. High-risk populations require lifelong supplementation and food fortification with vitamin D or calcium. Future research should identify the true prevalence of rickets and osteomalacia, their role in bone fragility and infant mortality, and best screening and public health prevention tools.

The classical clinical consequence of vitamin D deficiency is osteomalacia, presenting as rickets in children. This remains a common problem in parts of the Middle East and the Indian subcontinent, and occurs when serum 25-hydroxyvitamin D levels are <25 nmol/L. Osteomalacia remains the only problem that is unequivocally a consequence of vitamin D deficiency. Low levels of 25-hydroxyvitamin D are observed in a wide range of conditions, but consistent trial evidence of amelioration of these conditions with vitamin D is lacking. Monotherapy with vitamin D has not been found to be effective in meta-analyses of trials assessing its effects on bone density, fractures or falls. At present, supplements should be advised for individuals at risk of having serum 25-hydroxyvitamin D levels in the 25-40 nmol/L range, or below, with a view to prevention of osteomalacia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Calcium and phosphorus represent building material for bones. The supplier of these bone minerals is the hormone calcitriol, which originates from vitamin D, itself made by sunshine in human skin. Requirement for bone minerals is highest during phases of rapid growth, and no one grows faster than the foetus and the infant, making them particularly vulnerable. Deprivation of calcium, whether through low calcium intake or low vitamin D, leads to serious health consequences throughout life, such as hypocalcaemic seizures, dilated cardiomyopathy, skeletal myopathy, congenital and infantile rickets, and osteomalacia. These 5 conditions are often summarised as 'symptomatic vitamin D deficiency', are fully reversible but also fully preventable. However, the increasing prevalence of rickets and osteomalacia, and the deaths from hypocalcaemic cardiomyopathy, demand action from global health care providers. Clarification of medical and parental responsibilities is a prerequisite to deliver successful prevention programmes. The foetus and infant have the human right to be protected against harm, and vitamin D supplementation has the same public health priority as vaccinations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The case of a recurrent phosphaturic mesenchymal tumour of the maxillary sinus 10 years after the first surgical excision is reported. The neoplasm first presented with paraneoplastic osteomalacia causing a pathological femur fracture. A right maxillary sinus tumour was identified and treated thereafter. The patient had no local symptoms and serum electrolytes returned to normal after surgical removal of the tumour. However, 10 years later, the patient's urine Ca and P levels increased and an octreoscan detected a new tumour in the right maxillary sinus. Early diagnosis prevented the effects of the paraneoplastic activity of the neoplasm. This case emphasises the importance of specific, close follow-up, because the neoplasm rarely produces local signs indicating its position. To our knowledge, this is the first reported case of a late relapse presenting without relevant symptoms (local pain or swelling or pathological fractures)., (2014 BMJ Publishing Group Ltd.)

Context: Bone health is influenced by the intake of both calcium and vitamin D., Objective: Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover. SETTING, PATIENTS, AND DESIGN: At an ambulatory research center, 159 postmenopausal healthy white women participated in this double-blind, placebo-controlled parallel, longitudinal factorial study that was 6 months in duration., Interventions: Subjects were randomly allocated to 4 groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D3 (100 μg) plus placebo, and 4) vitamin D3 and calcium. Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months., Main Outcome Measures: Serum PTH, cross-linked C-telopeptide (CTX), and procollagen type I N-terminal propeptide (P1NP) were measured., Results: Before study medication, a calcium load resulted in a decline in PTH and CTX and an increase in urinary calcium excretion. Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake. There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo. Suppression of PTH was greater after a calcium load in the vitamin D groups. A calcium load decreased PTH and CTX and raised urinary calcium., Conclusions: Fasting PTH declines with vitamin D supplementation. PTH declines after calcium intake. Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers, whereas supplementation with up to100 μg vitamin D3/d does not.

Vitamin D is important for the normal development and maintenance of bone. The elucidation of the vitamin D activation pathway and the cloning of the vitamin D receptor have advanced our understanding of the actions of vitamin D on bone. The preponderance of evidence indicates that 1,25(OH)₂D₃ enhances bone mineralization through its effects to promote calcium and phosphate absorption. Although 1,25(OH)₂D₃ stimulates bone resorption in vitro, treatment in vivo can prevent bone loss and fracture through several potential mechanisms. The development of vitamin D analogues has provided new therapeutic options for increasing bone mineral density and reducing fractures., (Copyright © 2012 Elsevier Inc. All rights reserved.)

All cells comprising the skeleton-chondrocytes, osteoblasts, and osteoclasts-contain both the vitamin D receptor and the enzyme CYP27B1 required for producing the active metabolite of vitamin D, 1,25 dihydroxyvitamin D. Direct effects of 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D on these bone cells have been demonstrated. However, the major skeletal manifestations of vitamin D deficiency or mutations in the vitamin D receptor and CYP27B1, namely rickets and osteomalacia, can be corrected by increasing the intestinal absorption of calcium and phosphate, indicating the importance of indirect effects. On the other hand, these dietary manipulations do not reverse defects in osteoblast or osteoclast function that lead to osteopenic bone. This review discusses the relative importance of the direct versus indirect actions of vitamin D on bone, and provides guidelines for the clinical use of vitamin D to prevent/treat bone loss and fractures.

Background: Measuring serum 25(OH)D concentration is common in clinical practice despite the questionable reliability of assays., Aims: The aim of the present study was to examine agreement in 25(OH)D concentrations measured by different assays and laboratories, and consider related clinical implications., Methods: Serum samples from 813 participants in the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study) were assayed for 25(OH)D concentration. Duplicate samples from subsets of subjects were sent to different laboratories, two using DiaSorin Liaison (Laboratory A and B) and one using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS - selected here as the nominal gold standard). Pairwise within-assay (both within-laboratory and between-laboratories) and between-assay agreement was examined using Deming regression and Bland-Altman plots. Common 25(OH)D cut-points for classification of vitamin D deficiency were used to compare the different assays., Results: 25(OH)D concentrations measured using Liaison were substantially lower at Laboratory A than at Laboratory B (mean bias -11.60 nmol/L, 95% limits of agreement -46.39, 23.18). Both Liaison assays returned much lower 25(OH)D concentrations than LC-MS/MS (mean bias up to -26.05 nmol/L, 95% limits of agreement of -13.21, 65.31). For Laboratory A participants, 46% (355/765) were classified as vitamin D deficient (25(OH)D <50 nmol/L) using Liaison compared with 17% (128/765) using LC-MS/MS. For Laboratory B participants, the respective figures were 36% (76/209) and 20% (41/209). Hence, between 1-in-5 and 1-in-3 participants were misclassified as 'deficient'., Conclusion: Bias and variability in 25(OH)D measurements sufficient to affect significantly clinical decision-making were found both between-laboratories and between-assays. The adoption of common standards to allow assay calibration is required urgently., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Fibroblast growth factor-2 (FGF2) has been demonstrated to be a promising osteogenic factor for treating osteoporosis. Our earlier study shows that transplantation of mouse Sca-1(+) hematopoietic stem/progenitor cells that are engineered to express a modified FGF2 leads to considerable endosteal/trabecular bone formation, but it also induces adverse effects like hypocalemia and osteomalacia. Here we report that the use of an erythroid specific promoter, β-globin, leads to a 5-fold decrease in the ratio of serum FGF2 to the FGF2 expression in the marrow cavity when compared to the use of a ubiquitous promoter spleen focus-forming virus (SFFV). The confined FGF2 expression promotes considerable trabeculae bone formation in endosteum and does not yield anemia and osteomalacia. The avoidance of anemia in the mice that received Sca1(+) cells transduced with FGF2 driven by the β-globin promoter is likely due to attenuation of high-level serum FGF2-mediated stem cell mobilization observed in the SFFV-FGF2 animals. The prevention of osteomalacia is associated with substantially reduced serum Fgf23/hypophosphatemia, and less pronounced secondary hyperparathyroidism. Our improved stem cell gene therapy strategy represents one step closer to FGF2-based clinical therapy for systemic skeletal augmentation.

Paget's disease of bone (PDB) is the second most common metabolic bone disease. Bisphosphonates (BPs) are currently the drugs of choice for PDB. PDB and osteomalacia are both common in the elderly. The concept of relative vitamin D deficiency in patients with PDB was suggested long ago, but it has not yet elucidated. Both diseases predispose to fractures, but their combined action to fragility has not been studied yet. The older BPs, mainly etidronate, further inhibit bone mineralization. Mineralization defects have also been described in patients with PDB treated with pamidronate. Moreover, hypocalcemia and secondary hyperparathyroidism after treatment with BPs have been described in PDB. Hypocalcemia seems to be more severe after treatment with the more potent, intravenous zoledronic acid, which is currently the treatment of choice for PDB. The counteracting hyperparathyroidism pathophysiologically intends to increase renal reabsorption of calcium and 1.25-dihydroxy vitamin D production and to stimulate osteoclasts in order to prevent long-term hypocalcemia. However, the effect of PTH on osteoclasts is, at least partly, restricted in patients taking BPs. Secondary hyperparathyroidism is a potentially detrimental condition, especially in patients already suffering from another bone disease. Serum calcium and vitamin D deficiency should be restored before BP treatment and calcium and vitamin D administration should be possibly continued for longer after achieving normocalcemia, which may shorten the duration of secondary hyperparathyroidism. QUICK SUMMARY: Mineralization defects and hypocalcemia with secondary hyperparathyroidism have been described in patients with Paget's disease of bone treated with bisphosphonates. Secondary hyperparathyroidism may be a potentially detrimental condition for patients with Paget's disease of bone., (© J. A. Barth Verlag in George Thieme Verlag KG Stuttgart · New York.)

Background: Hyperthyroidism is associated with bone loss, which is reversible after treatment. The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment especially at forearm is not clear. Therefore, the present study was conducted to assess degree of reversibility in bone mineral density following one-year medical treatment in Indian patients with hyperthyroidism., Methods: A total of 30 consecutive patients with hyperthyroidism were included in this one year study at All India Institute of Medical Sciences, New Delhi, India. All the patients were assessed for parameters of bone mineral homeostasis such as calcium, phosphorous, alkaline phosphatase, 25-hydroxy vitamin D [25 (OH) D], parathyroid hormone (PTH) at the time of diagnosis and after one year medical treatment. Bone mineral density was measured using Hologic DXA scan at hip, spine and forearm. All the patients received medical therapy with carbimazole. The parameters of bone homeostasis and bone mineral density at base line and after one year medical treatment was compared., Results: All patients attained euthyroid status after eight weeks of carbimazole therapy. Parameters of bone homeostasis such as calcium, phosphorous, 25 (OH) D and PTH did not show any significant change from base line. Bone mineral density expressed as bone mineral content in gm/cm2 at left hip neck, trochanteric and intertrochanteric region was significantly higher after carbimazole therapy (745.2 +/- 127.6 gm/cm2 vs. 688.2 +/- 123.5 gm/cm2; p = 0.02, 573.4 +/- 109.9 gm/cm2 vs. 641.0 +/- 138.0 gm/cm2, p = 0.005 and 1008.6 +/- 185.5 gm/cm2 vs. 938.0 +/- 145.3 gm/cm2 p = 0.0131 respectively). Bone mineral density at lumbar spine expressed as either T and Z score was significantly higher after treatment (10 months of euthyroid state) (-0.6 +/- 1.3 vs. -1.7 +/- 1.2, p = 0.013 and -0.4 +/- 1.2 vs. -1.4 +/- 1.2, p = 0.012 respectively). However Bone mineral measures as T and Z score at left forearm decreased significantly after one year of medical therapy., Conclusion: In Indian patients with hyperthyroidism, the pattern of recovery of bone loss after one year of antithyroid therapy suggests early recovery at hip and lumbar spine and deterioration at forearm.

Vitamin D deficiency causes rickets in children and osteomalacia in adults. These are common today but often not recognized. This article summarizes the clinical features, investigation and treatment of these disorders and examines the factors contributing to failures of diagnosis.

Highly active antiretroviral therapy (HAART) has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV). HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.

A number of drugs can have "side effects" on bone metabolism and formation, causing bone atrophy, impaired mineralisation, as well as osteonecrosis. In both clinical and general practitioner settings, these forms of bone damage have been hitherto considered as adverse drug side effects and have received insufficient attention; moreover, they have not been the subject of patient information. Preventive measures are not instigated prior to initiation of medication and even after onset of bone damage, therapeutic strategies are poorly implemented. Even fracture healing with its complex, staged course can be both positively and negatively influenced by a number of drugs and these effects require monitoring. Recommendations regarding practical screening and therapy of drug-induced osteopathies are presented.

Background: Long-term therapy with antiepileptic drugs (AED) may be associated with increased total serum alkaline phosphatase (ALP) levels and reduced serum calcium, inorganic phosphorous, and vitamin D levels. These adverse biochemical alterations have an adverse effect on bone health., Objective: To determine (a) onset of derangements in serum total ALP and its isoenzymes (liver, bone), calcium and 25-hydroxy vitamin D (25-OHD) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy and (b) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance (RDA) dosage, on these biochemical parameters., Materials and Methods: Study was a prospective, case-controlled study in adults. Serum biochemical parameters were estimated at baseline, 30, 60, and 90 days of starting AED treatment in the study subjects: Groups--A (only calcium supplementation) and Group B (both calcium and 25-OHD supplementation)., Statistical Analysis: Mean+/-SD, and students' paired t test (between groups A and B) unpaired students' t test (drug-wise)., Results: At 60 days of AED therapy Group A showed a significant increase in serum total ALP (78.83+/-11.04 to 101.75 +/- 9.56 IU/l) (P < 0.001), ALP-liver isoenzyme, (41.97+/- 10.81 to 68.83 +/-7.81 IU/L) (P < 0.001), significant decrease in calcium (9.30 +/- 0.36 to 8.80 +/- 0.38 mg%) (P < 0.001), ALP-bone isoenyzme (36.84 +/- 5.01 to 32.92 +/- 6.46 IU/L) (P < 0.001), and a significant decrease in 25-OHD (25.19 +/- 5.98 to 19.76 +/- 5.35 ng/ml) (P < 0.001) at 90 days. In contrast Group B, at 60 days, showed a significant decrease in serum total ALP (81.92 +/- 19.63 to 54.77. +/- 11.53 IU/L) (P < 0.0001), ALP-liver isoenzyme (48.01. +/- 13.53 to 28.12. +/- 5.88 IU/L) (P < 0.0001), significant increase in calcium ((9.24 +/- 0.31 to 9.93 +/- 0.26 mg%) (P < 0.001) and ALP-bone isoenzyme levels (33.93 +/- 12.2 to 26.25 +/- 8.23 IU/L). In Group B, 25-OHD levels showed a significant increase at 90 days (24.36 +/- 3.42 to 31.53 +/- 327 ng/ml) (P < 0.0001)., Conclusion: Biochemical derangements in calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy, indicating predisposition to development of osteomalacia in these patients. This is preventable by simultaneous oral supplementation with calcium and 25-OHD.

Mice lacking 25-hydroxycholecalciferol [25(OH)D]-1alpha-hydroxylase (CYP27B1) are growth retarded, hypocalcemic, and have poor bone mineralization. We tested whether high dietary cholecalciferol (VD3) could exert effects in the absence of CYP27B1 in vivo. Weanling male wild-type (WT) and CYP27B1 knockout (KO) mice were fed either a 2% calcium (Ca), 20% lactose rescue diet or an AIN93G diet (0.5% Ca, 0.4% phosphorus) containing 1000 (1K, the rodent requirement, 25 microg), 10,000 (10K, 250 microg), or 20,000 (20K, 500 microg) IU VD3/kg diet until 12 wk when blood and tissues were taken. Serum 25(OH)D was >90 nmol/L in the 1K diet group and increased >4-fold in mice fed 10K and 20K diets. The 1K diet impaired growth and caused hypocalcemia in KO mice; the 10K and 20K diets were as effective as the high Ca rescue diet in preventing these outcomes. High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D(9K)) and kidney (CYP27B1, 24-hydroxylase, calbindin D(9K)) of KO mice. Micro-computed tomography of femora revealed complete recovery of cortical bone in KO mice fed either the rescue or 10K diets but only partial recovery of trabecular bone measures (e.g. 40% lower bone volume, 20% lower trabecular thickness, and 23% increase in trabecular separation). These data show that very high serum 25(OH)D can influence Ca and bone metabolism independent of its conversion to 1,25 dihydroxycholecalciferol. However, neither high dietary Ca nor high dietary VD3 is sufficient to fully recover the phenotype of CYP27B1 KO mice.

Published reports of studies on the long-term effects of anti-epileptic drugs (AED) on bone--its density, thickness, vitamin D metabolism and risk of fracture--have shown considerable methodological inadequacies (34). Despite these problems it has been clearly shown that patients with epilepsy who are on anti-epileptic drugs have a greater than normal risk of bone loss, abnormal mineralization and fractures. A patient on long-term treatment with AED has a two- to three-fold risk of sustaining a fracture. On average 50% of patients (ranging from 4-70% in different studies [18]) have an osteopathy (34). Type, dosage and duration of AED treatment determine the exact picture of the osteopathy--regardless of whether or not they are enzyme-inducing. Among the enzyme-inducing drugs, especially phenytoin, primidone, phenobarbital and carbamezapine have been investigated for their influence on vitamin D metabolism. Bone loss has also been noted even without evidence of vitamin D deficiency. Mixed forms of osteoporosis and osteomalacia occur particularly often and must be taken into account in any differentiated form of treatment. But the question remains unanswered whether current AEDs, such as lamotrigine, gabapentin or levetiracetam will cause little or no osteopathy. Comparable to the situation during long-term systemic administration of glucocorticoids, initial diagnosis, including the inexpensive dual-energy X-ray absorptiometry (DXA) and the serum concentration of 25-hydroxyvitamin D, must be obtained to determine whether initially there are any bone changes. In addition to a differentiated and clearly defined treatment of osteopathy in a patient with epilepsy, the aim must be to minimize the tendency towards seizures and their severity. The annual cost of adequate vitamin D substitution is about EUR 50, while biphosphonate treatment costs about EUR 500; the costs of vertebral or forearm fractures are about EUR 1000 and those of hip fracture about EUR 15,000. These figures exclude the costs of rehabilitation, nursing care and loss of earnings. Looked at in this way, the problem of AED-induced osteopathy has been underestimated. Yet it is actually preventable and--if already present--can be efficaciously and inexpensively treated when the new guidelines of the (German) Joint Organization of Osteology are followed. The prerequisite of rational treatment is a diagnostically clear distinction of osteoporosis and osteomalacia, but mixed forms are common. ("osteoporomalacia"). Further investigations of more recently developed AEDs (e.g. gabapentin, lamotrigine or levetiracetam) regarding their damaging action on bone during their long-term administration is essential. Systematic control of the state of bones in all patients on long-term treatment with AEDs is nowadays recommended without qualification, even though some study data are unsatisfactory or even lacking.

Vitamin D deficiency is a relevant problem particularly in south Europe and in over 65 year old subjects, that is often underestimated. Vitamin D deficiency represents a real medical emergency also for its role in the patho-physiology of muscular-skeletal diseases. Chronic vitamin D deficiency leads to severe bone and muscular outcomes including: osteoporosis, osteomalacia and proximal limb myopathy. These increase the risk of falling and fractures. The efficacy of vitamin D treatment in decreasing the fracture risk has been reporting in several studies. The negative results of some recent studies questioned the clinical vitamin D efficacy. However these studies have a number of methodological problems and even the interpretation of the results is questionable. In this paper we review all these aspects. This analysis permits to confirm that vitamin D treatment can be extremely cost-effective when given to people at high risk of deficiency. An acceptable compliance is obviously of critical importance.

The primary goal in the practical management of osteoporosis is to prevent first or subsequent fractures and thereby to avoid acute or chronic pain and progressive skeletal deformity. Therapeutic strategies should always take the complex pathogenetic mechanisms of fractures into account, especially the fact that mechanical impacts and falls play an important role in the majority of fracture events. Accordingly, recommendations to patients and the selection of drugs should aim at both, falls and fractures. In this context there is an increasing interest in the dual effects of vitamin D on bone and muscle. Controlled studies proved that adequate vitamin D supplementation is able to improve muscle strength, coordination and body sway and thereby reduce the risk of falls and fractures. Alendronate has been studied extensively by large trials of high quality and its efficacy to reduce the risk of vertebral and nonvertebral fractures is in line with the criteria of evidence-based medicine. The innovative combination of 70 mg alendronate with 2,800 IU vitamin D in a once-weekly tablet guarantees a basic supply with this important prohormone for bone and muscle. Due to a regular combined intake an improved compliance can be anticipated which will be followed by better therapeutic results in osteoporosis patients with increased fracture risk.

Recent studies have added new dimensions to the fund of knowledge on vitamin D. In addition to the classic role of vitamin D in preventing rickets and osteomalacia, a preventive effect against osteoporotic fractures has been convincingly established, and abundant evidence suggests a role in preventing malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple test for evaluating vitamin D status. However, recent review articles indicate that current reference ranges for serum 25-OH-vitamin D are too low. An appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml). Standard supplement dosages may fail to provide concentrations above this range.

Endogenous vitamin D deficiency (low serum 25(OH)D3) is a necessary but insufficient requirement for the genesis of vitamin D-deficiency rickets and osteomalacia. The magnitude of the independent contributions of dietary factors to rachitic and osteomalacic risk remains uncertain. We reanalysed two weighed dietary surveys of sixty-two cases of rickets and osteomalacia and 113 normal women and children. The independent associations of four dietary variables (vitamin D, Ca, fibre and meat intakes) and daylight outdoor exposure with rachitic and osteomalacic relative risk were estimated by multivariate logistic regression. Meat and fibre intakes showed significant negative and positive associations respectively with rachitic and osteomalacic relative risk (RR; zero meat intake: RR 29.8 (95 % CI 4.96, 181), P<0.001; fibre intake: RR 1.53 (95 % CI 1.01, 2.32), P=0.043). The negative association of meat intakes with rachitic and osteomalacic relative risk was curvilinear; relative risk did not fall further at meat intakes above 60 g daily. Daylight outdoor exposure showed a significant negative association with combined relative risk (RR 0.33 (95 % CI 0.17, 0.66), P<0.001). Operation of the meat and fibre risk factors was related to sex, age and dietary pattern (omnivore/lactovegetarian), mainly determined by religious affiliation. The mechanism by which meat reduces rachitic and osteomalacic risk is uncertain and appears independent of revised estimates of meat vitamin D content. The meat content of the omnivore Western diet may explain its high degree of protection against nutritional rickets and osteomalacia from infancy to old age in the presence of endogenous vitamin D deficiency.

Epidemiological studies have indicated incidences of 32.9% and 27.8% for rickets and osteomalacia, respectively, in Bactrian camels (Camelus bactrianus), but there is an increased incidence under drought conditions, sometimes reaching 75%. We have found that concentrations of phosphorus and copper in forage and soil samples in a drought affected area were significantly lower than in a control area or normal reference values (P < 0.01) ; the mean Ca:P ratio in the forages was 50:1. The phosphorus content of blood and hair from affected camels was significantly less than that in controls (P < 0.01) and concentrations of copper in the liver and kidney were significantly lower in affected camels than control animals (P < 0.01); the concentrations of triiodothyronine (T(3)), thyroxine (T(4)) and parathyroid hormone (PTH) in the serum from affected animals were significantly higher than those from healthy controls (P < 0.01); serum inorganic phosphorus and ceruloplasmin levels were lower than those in the controls (P < 0.01 or P < 0.05); the concentrations of serum alpha-globulin and beta-globulin were significantly higher in the affected camels than in the healthy controls (P < 0.01). The pathological changes seen in camels affected with rickets included porous, brittle, light, osteoporotic bones that were susceptible to fractures and had less resistance to cutting and sawing. Wrist joints were enlarged with an apparent bowing of the long bones in forelimb and with typical broadening of the epiphyses. In adult female camels, many enlarged scars were often seen in ribs indicating earlier fractures. The disease could be cured with supplementary bone meal, phosphate or mineral mixtures and in field investigations clinical signs disappeared within 15 days. Over the same period, the concentrations of phosphorus and alkaline phosphatase in blood returned to normal. The disease may be effectively prevented by use of mineral blocks (block salt licks) or dosing orally with copper, selenium and cobalt soluble glass boluses. We conclude that rickets and osteomalacia are mainly caused by phosphorus and copper deficiencies in the pasture.

Unlabelled: Complete androgenic blockade used in the treatment of advanced prostatic carcinoma can be attained by administration of antiandrogens in orchidectomized patients or by combined therapy with LH-RH analogs and antiandrogens. The treatment, however, decreases the influence of both androgens end estrogens on bone tissue and may result in bone mass loss and increased propensity to fractures. The purpose of the study was to determine the influence of complete androgenic blockade on bone mass and skeletal metabolism in men with advanced prostatic carcinoma and to assess whether 1alpha-OH vitamin D3 (1alpha-OHD3) together with calcium supplementation is able to prevent bone mass loss in men treated with complete androgenic blockade. 51 patients with advanced prostatic carcinoma, with skeletal metastases, aged 44 - 86, mean 68 ys were included into a 12-month prospective study. All patients were treated with orchidectomy followed by therapy with flutamide in a dose of 750 mg daily. 26 patients were additionally given 1alpha-OHD3 in a dose of 0.5 microg/d and calcium carbonate in an initial dose of 1 g daily. It was found that the 12-month treatment with complete androgenic blockade resulted in a decrease in bone mineral density (BMD) by 8.1% in the lumbar spine, by 6.3% in the femoral neck and by 3.5% in the total skeleton. Therapy with 1alpha-OHD3 and CaCO3 caused complete inhibition of bone tissue loss in the lumbar spine and resulted in an increase in BMD by 2.2% in femoral neck and by 1.9% in the total skeleton. None of the examined patients experienced any skeletal fractures. In both groups of patients a prompt decrease in serum alkaline phosphatase activity - a marker of osteoblast activity and an increase in fasting urine calcium creatinine ratio indicating acceleration of bone resorption were found., Conclusions: in patients with advanced prostatic carcinoma treated with complete androgenic blockade acceleration of bone mass loss is observed; treatment with 1alpha-OHD3 and CaCO3 is able to prevent both trabecular and compact bone loss.

Background: Inadequate serum vitamin D is associated with secondary hyperparathyroidism, increased bone turnover, and bone loss, which increased fracture risk. Osteomalacia has also been observed in severe cases. Indeed, vitamin D and calcium are essential components of management strategies for the prevention and treatment of osteoporosis. Despite this, many people currently do not have adequate vitamin D levels. This problem has been documented in many studies around the world, regardless of age, health status, or latitude, and is especially common among older adults, who are also likely to have osteoporosis. Factors that contribute to low vitamin D include low exposure to sunlight, decreased synthesis in skin and reduced intestinal absorption related to aging, and limited dietary sources. Supplementation is the most effective means of correcting poor vitamin D nutrition. However, few patients with osteoporosis currently take sufficient vitamin D supplements., Scope: This review article discusses the role of vitamin D in osteoporosis and skeletal health, and summarizes what is known about the high prevalence of inadequate serum vitamin D and recommendations for supplementation., Conclusion: Greater awareness of the importance of vitamin D for skeletal health and more aggressive supplementation efforts are urgently needed to address this important public health problem.

Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations are currently recognized as the functional status indicator for vitamin D. Evidence is reviewed that shows that serum 25(OH)D3 concentrations of < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk. For typical older individuals, supplemental oral intakes of approximately 1300 IU/d are required to reach the lower end of the optimal range. Evidence of substantial problems in routine clinical measurement of serum 25(OH)D3 concentrations among patients is cited. There is great need for standardization and improved reproducibility and sensitivity of measurements of serum 25(OH)D3 concentrations.

Antiepileptic drugs (AEDs) are associated with bone disease. Early reports found rickets in children and osteomalacia in adults, but those reports were primarily in institutionalized persons. Studies in ambulatory adults and children taking AEDs do not reveal rickets or osteomalacia but do report abnormalities in biochemical indexes of bone mineral metabolism and density. In addition, fracture rates are increased in AED-treated patients. AEDs that induce the cytochrome P450 enzyme system are most commonly associated with abnormalities in bone. Emerging data suggest that valproate, an enzyme inhibitor, may also affect bone, and there is limited information on the newer AEDs. Several theories on the mechanism of AED-associated bone disease have been proposed, but no single one explains all the reported findings. Identifying AED-treated patients who are at risk for or have bone disease is important, as multiple therapies are available.

Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.

Sun is at the origin of life. It can also be responsible for death. In the past decades cutaneous melanoma killed more and more young adults. Currently, the disease still progresses in the population, but survival increases hopefully. Sun is pointed out as the main culprit. Hence, protection against harmful effects of ultraviolets is mandatory. However, preventive measures to be taken generate heated scientific argument. Sunlight exposure particularly in moderation is indeed necessary for health through vitamin D3 synthesis and psychological effects on wellbeing. Vitamin D3 provides numerous biological effects, particularly on bone calcification and also by inhibiting proliferation and migration of malignant cells including melanoma cells. Hence, we are facing the dilemma between too much and too little ultraviolet light exposure. Anyway, one cannot advocate that people lie in the sun until they burn or until they turn a rich brown complexion.

A 59-year-old woman presented with a 3-month history of bilateral, proximal lower-limb weakness associated with disabling pain that rendered her wheelchair-bound. There were no gastrointestinal symptoms. Clinical examination showed evidence of bilateral, proximal muscle atrophy and weakness in the lower limbs. Low serum calcium and raised serum alkaline phosphatase, coupled with radiological findings, led to the diagnosis of osteomalacia. Subsequent gastroscopy and duodenal biopsy confirmed a diagnosis of coeliac disease. With adherence to a gluten-free diet, the patient's condition remarkably improved within 3 months and she could walk pain-free using a stick. Osteomalacia and myopathy may rarely be the initial and primary presentations of coeliac disease. There are very few reports of osteomalacia as the only presentation of coeliac disease and no reports that describe such a dramatic recovery 3 months after commencing a gluten-free diet. A review of the literature regarding osteomalacia and myopathy in coeliac disease is presented.

The incidence of parenteral nutrition-associated metabolic bone disease is unknown. Initial reports from the early 1980s suggested that both osteoporosis and osteomalacia were quite common in patients who receive long-term parenteral nutrition. The findings described in these early surveys provide a snapshot into the many factors that contribute to the development of metabolic bone disease. More recent evidence suggests that bone loss may not be as great with the initiation of parenteral nutrition as once was thought, and that most of the metabolic bone disease that is noted may be related to the patient's underlying illness. Although this recent information is reassuring, it is of the utmost importance to provide parenteral nutrition that minimizes further bone loss and promotes the formation of new bone. This review will describe the general features of metabolic bone disease and the abnormalities noted with parenteral nutrition-associated metabolic bone disease, highlight the importance of preexisting illness and parenteral nutrition associated factors that contribute to the development of metabolic bone disease, and finally discuss an approach to avoid this debilitating complication of long-term parenteral nutrition.

Objective: To review experiences of nutritional rickets and osteomalacia in school children and adolescents at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia., Methods: Records of children and adolescents aged 6-18 years, seen at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, during the period January 1994 through to December 1999, who were diagnosed to have rickets or osteomalacia were reviewed. The diagnosis was based on clinical, biochemical and radiological data. Data extracted and analyzed included age, sex, presenting symptoms and signs, dietary history and sun exposure, blood count, bone profiles, renal and liver profile, and 25-hydroxy vitamin D3 and 1, 25 dihydroxy vitamin D3. Hand and wrist x-rays were carried out for all patients while bone density of lumbar spine and 3 femoral sites and bone scan were performed on the majority of patients., Results: Forty-two children and adolescents (25 females and 17 males) were diagnosed. Their age ranged between 6-18 years with a mean of 13.5. Non specific symptoms, such as bone pain and fatigue were the most presenting symptoms, while skeletal deformities and fractures were the presenting symptoms in only 5 and 3 patients. Lack of direct sun exposure and poor calcium intake was evident. Bone profiles at the time of diagnosis revealed mean serum calcium of 2.1 mmol/L, range 1.5 2.3 (Normal=2.2-2.7), phosphorus 1.1 mmol/L, range 0.7 1.9 (Normal=1.4 2.1) and alkaline phosphatase activities of 1,480 U/L, range 834-2,590 (N=<600). Serum concentrations of 25-hydroxy Vitamin D were low (<10 mg/L) while that of 1, 25 Dihydroxy Vitamin D varied between low to normal (<10-45 ng/L). Bone density of the lumbar spine and 3 femoral sites were performed in 26 patients and showed markedly reduced values, while bone scan demonstrated a high uptake of tracer throughout the skeleton "super scan". Multiple stress fractures were evident in 8 children., Conclusion: Although a community-based study to assess the magnitude of the problem is needed, it seems that rickets and osteomalacia of nutritional origin are not that uncommon and deserves special attention from all pediatricians and practicing physicians. They also suggested that further studies are needed to help understand the pathophysiology, and identify the contributing factors for the development of the disorder.

The aim of the study is to compare vitamin D status and bone mineral density (BMD) in veiled and unveiled healthy Turkish women of reproductive age. Thirty young to middle-aged volunteer veiled women and 30 age-matched control subjects with western clothing habits were enrolled in the study. The two groups had similar dietary habits, body mass index (BMI) distribution, and gestational history. Physical and laboratory examinations were performed to rule out any disease that could affect bone metabolism. Serum 25-hydroxyvitamin D (25-OHD) levels were measured, and BMD of the spine and hip were investigated by dual energy x-ray absorptiometry (DEXA). The mean age of dressing the veil was 15.7 +/- 6.13 years, and 66.7% of the veiled women claimed that they were not ever exposed to direct sunlight, as they were leading an indoor life. Compared with the control group, veiled women were less educated and physically less active (p < 0.001 and p < 0.05, respectively). 25-OHD levels were positively correlated with exposure to sunlight and negatively correlated with the duration of being veiled. None of the veiled women had vitamin D insufficiency, but their mean 25-OHD concentration (33.1 +/- 16 ng/ml) was significantly lower than that of controls (53.9 +/- 27.3 ng/ml) (p < or = 0.001), and serum alkaline phosphatase (ALP) levels were higher (p < 0.01). Differences in the absolute BMD values at the spine and hip were not statistically significant, but the mean Z value at the lumbar spine was significantly lower in the veiled subjects (p < 0.05). Veiled women have low 25-OHD status, and vitamin D supplementation should strictly be advised to these women for the prevention of osteomalacia and osteoporosis.

CONTRACEPTION: As in women who do not have a heart transplant, contraception is never perfect, irrespective of the method, intrauterine device (risk of infection), estrogens, progestogens. PREGNANCY: Besides the general effects also observed in all pregnant women, pregnancy in the heart transplant recipient also carries the risk of cytomegalovirus infection and preeclampsia., Immunosuppression: Cyclosporin or azathioprine are generally indicated, depending on the individual risks. PREVENTION OF BONE DISEASE: Advice concerning diet and lifestyle should be given prior to transplantation in order to reduce the risk of osteoporosis and osteomalacia. Bone density, particularly of the femoral neck, is essential for screening. A rheumatology examination is also quite useful., Cancer: De novo cancer is favored by the use of antilymphocyte inductors. Most are breast cancers (mean delay 60 months); other gynecology cancers develop after about 50 months. The risk of recurrence in patients who had breast cancer is highest during the first 2 years. The risk of recurrent uterine cancer is constantly observed.

Vitamin D deficiency is relatively common among older persons and those with spinal cord injuries. We report a case of proximal renal tubular acidosis in a 44-year-old quadriplegic nursing home resident who had limited sunlight exposure. Laboratory studies showed a low level of serum bicarbonate, a normal serum anion gap, and a positive urine anion gap. There was no history of diarrhea. Serum calcium and phosphorus levels were 6.9 mg/dL and 3.7 mg/dL, respectively. Proximal renal tubular acidosis due to osteomalacia was suspected, which was confirmed by a low serum 25-hydroxycholecalciferol level (< 5 ng/mL) with an elevated serum parathyroid hormone level. Treatment with vitamin D and a calcium supplement led to normalization of laboratory values.

The aim of the present study was to clarify the therapeutic effects of 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 microg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats.

Background: The objective of the study was to evaluate bone mass status (as measured by bone ultrasound) in patients on anticonvulsant therapy, and the influence that Vitamin D administration exerts over it., Materials and Methods: We measured and compared the basal serum levels of 25(OH)D3, parathyroid hormone (PTH), and phalangeal bone ultrasound (Ad-SOS), in 30 adult patients who were taking anticonvulsant drugs, with a control group of similar age and sex. We then gave the patients a large oral dose of 3 mg (120.000 UI) of 25(OH)D3, and repeated the measurements after one month., Results: Basal 25(OH)D3 and Ad-SOS values were significantly lower, and PTH values significantly higher (P< 0.0001 in all), in the patient group. The low Ad-SOS values for the patients were independent of the treatment, but directly related to basal 25(OH)D3 levels (r = 0.45, P<0.01). There was a negative association between PTH and 25(OH)D3 (r = -0.64, P<0.0001), and no correlation between PTH y Ad-SOS (r = -0.20, p NS). After ingestion of the large dose of the vitamin D, the patient group registered a significant (P<0.0001) increase in 25(OH)D3 levels, their Ad-SOS values increased (P<0.0001) nearly to the mean basal value of the control group, and PTH decreased significantly (P<0.0001)., Conclusions: These findings justify the need to assure adequate vitamin D intake in patients being treated with anticonvulsants, independently of the treatment, age, sex, and activity status, in order to prevent osteomalacia.