Risk Factors For Bone Disease Research Articles

Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia.

Diabetes mellitus (DM) has been shown to be a clinical risk factor for bone diseases including osteoporosis and fragility. Bone metabolism is a complicated process that requires coordinated differentiation and proliferation of bone marrow mesenchymal stem cells (BMSCs). Owing to the regenerative properties, BMSCs have laid a robust foundation for their clinical application in various diseases. However, mounting evidence indicates that the osteogenic capability of BMSCs is impaired under high glucose conditions, which is responsible for diabetic bone diseases and greatly reduces the therapeutic efficiency of BMSCs. With the rapidly increasing incidence of DM, a better understanding of the impacts of hyperglycemia on BMSCs osteogenesis and the underlying mechanisms is needed. In this review, we aim to summarize the current knowledge of the osteogenesis of BMSCs in hyperglycemia, the underlying mechanisms, and the strategies to rescue the impaired BMSCs osteogenesis.

MTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.

The interplay between bone and glucose metabolism has highlighted hyperglycemia as a potential risk factor for bone diseases. With the increasing prevalence of diabetes mellitus worldwide and its subsequent socioeconomic burden, there is a pressing need to develop a better understanding of the molecular mechanisms involved in hyperglycemia-mediated bone metabolism. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that senses extracellular and intracellular signals to regulate numerous biological processes, including cell growth, proliferation, and differentiation. As mounting evidence suggests the involvement of mTOR in diabetic bone disease, we provide a comprehensive review of its effects on bone diseases associated with hyperglycemia. This review summarizes key findings from basic and clinical studies regarding mTOR's roles in regulating bone formation, bone resorption, inflammatory responses, and bone vascularity in hyperglycemia. It also provides valuable insights into future research directions aimed at developing mTOR-targeted therapies for combating diabetic bone diseases.

Abstract #1377932: An Inherited Metabolic Disorder That Masquerades as Osteoporosis

Hypophosphatasia is a rare genetic disorder caused by loss-of-function mutations in the ALPL gene, which encodes tissue non-specific alkaline phosphatase. The enzyme defect results in the accumulation of substrates like inorganic pyrophosphate, thereby inhibiting mineralization of bones and teeth. Clinical features include premature loss of deciduous teeth, bowed legs, lower extremity stress fractures, bone pain and impaired mobility. Serum alkaline phosphatase (ALP) is a marker of bone turnover. Low ALP, high serum vitamin B6 and high urine phosphoethanolamine are diagnostic hallmarks of hypophosphatasia. A 54-year-old lady was referred to the endocrinology clinic for severe osteoporosis, characterized by an olecranon fracture and low bone mineral density (T score -3.0 at the left femoral neck). Bone disease risk factors included premature menopause at age 38 years and maternal history of hip fracture. There was no personal or family history of recurrent fractures, impaired mobility, or unexplained tooth loss. Despite treatment with ibandronate, zoledronic acid and teriparatide, her bone mineral density declined over the course of a decade. Physical examination revealed low BMI (18.07 kg/m2), normal gait and intact muscle strength. Lab testing disclosed low serum alkaline phosphatase (ALP) 18 units/L [reference 45 to 117 units/L], high serum vitamin B6 131.8 nmol/L [reference 20.0 to 125.0 nmol/L] and high urine phosphoethanolamine 104 nmol/mg Cr [reference < 48]. ALP results prior to bisphosphonate exposure were unavailable. Vitamin D status, thyroid function, parathyroid hormone, corrected serum calcium, ceruloplasmin and zinc levels were normal. Exome sequencing identified a pathogenic heterozygous nonsense ALPL gene mutation, c.1282C >T (p.Arg428X). She was counselled to avoid bisphosphonate therapy indefinitely. ALP measurement was advised for her blood relatives since hypophosphatasia is an autosomal recessive or dominant disorder. With asfotase alfa, the only FDA-approved therapy for juvenile-onset hypophosphatasia, there have been no further fractures to date, and her mobility remains unimpaired. Hypophosphatasia can be mistaken for osteoporosis since both conditions present with low bone mineral density on DEXA scan. Furthermore, bisphosphonate therapy and hypophosphatasia are mutually exclusive entities that can present with low ALP. Thus, bisphosphonate exposure may pose a diagnostic quandary when distinguishing between osteoporosis and hypophosphatasia. This case highlights the importance of assessing ALP when evaluating osteoporosis with atypical features such as age of onset under fifty years, remarkably low bone mineral density, fracture(s), and inadequate response to anti-osteoporosis agents. Moreover, if ALP is low, some index of suspicion for hypophosphatasia ought to be maintained, even if dental or lower extremity bone symptoms are absent. Genetic testing is confirmatory. Bisphosphonate therapy and parathyroid hormone analogs are not established treatment modalities for hypophosphatasia. Instead, enzyme replacement with asfotase alfa is recommended.

LBODP073 Non-functioning Pituitary Macroadenoma Presenting As Osteopenia In A Male

Abstract Non-functioning pituitary macroadenomas (NFPAs) account for 14-54% of all pituitary adenomas. NFPAs are benign, but mass effects may lead to significant symptoms, including visual impairment and pituitary insufficiency, of which secondary hypogonadism is present in 75% of reported cases. Patients with hypogonadism may experience decreased bone density, libido, muscle mass/strength, and fatigue. We describe a patient who presented with osteopenia, in addition to atypical symptoms of secondary hypogonadism, associated with low testosterone levels. Further workup disclosed a large pituitary macroadenoma. A 56-year-old male presented to the clinic for a two-year history of diffuse joint pain. X-rays were significant for bone loss. This led to a bone density scan that showed osteopenia with a T score of -2.3 in the lumbar spine and left femoral neck. He had no prior history of fractures or loss in height. Risk factors for bone disease were only pertinent for history of osteoporosis in his mother. He was referred to endocrinology for further evaluation. Work up included normal vitamin D levels, 24-hour urine calcium excretion, morning cortisol, and TSH. Given the patient's osteopenia and additional complaints of decreased appetite, weight loss, fatigue, and muscle weakness, testosterone levels were checked and found to be low. Free testosterone level was 14.3 pg/ml with inappropriately low FSH and LH. Prolactin was normal at 12.5 ng/ml. He subsequently had an MRI brain which revealed a pituitary macroadenoma measuring 2. 0×2.4×2.4 cm with mass effect on the optic chiasm. However, the patient did not complain of headaches or visual disturbances and visual field testing was normal. He underwent transsphenoidal resection of the pituitary tumor which led to normalization of testosterone levels and resolution of all his symptoms. This case exemplifies how non-specific symptoms of hypogonadism and absence of mass effect symptoms can lead to a delay in diagnosis of NFPA. Typically, NFPAs are detected when they are large enough to cause symptoms of mass effect which, interestingly, were absent in this patient despite compression of the optic chiasm. Male hypogonadism increases the risk for bone disease. Thus, it is important to pursue work up for secondary hypogonadism in males presenting with osteopenia/osteoporosis despite lack of overt symptoms. A thorough history and workup are essential in diagnosing NFPA. Prompt detection of NFPA can facilitate timely management leading to clinical improvement. The first line of treatment for NFPAs causing neurological symptoms is transsphenoidal surgical resection. Surgery is also recommended for NFPAs that are at high risk for causing visual deficits due to involvement of optic chiasm, as was seen in this patient. Post-surgical follow up includes long-term routine monitoring of hormone levels and neuroimaging. Presentation: No date and time listed

Bone mineral density in spanish children at the diagnosis of inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been reported to be associated, even at disease onset, with low bone mass. The aim of this study was to know the bone mineral density (BMD) status in the IBD pediatric population of group of Spanish children, at the time of diagnosis. Retrospective review of patients' records from pediatric IBD patients diagnosed in our unit in the last 10years. BMD was measured at the time of diagnosis and was expressed by Z-score. Fifty-seven patients were included. Sixty-one percent were male and 47.4% had Crohn's disease (CD). Average age was 11.18 (SD 2.24) years old. Median BMD Z-score was - 0.30 (interquartile range: - 1.10 to + 0.10). Low BMD, defined as Z-score ≤ - 2SD, was present in 5% of patients, but there was no single patient with osteoporosis. There were no differences in BMD between Ulcerative Colitis (UC) and CD. Statistical differences appeared between healthy Spanish pediatric population and our IBD cohort, these having lower BMD for the same age and gender. A linear regression analysis showed a significant association between BMD Z-score and patient´s weight and height Z-score with a p values of 0.001 and 0.048, respectively. Suboptimal bone density is present at diagnosis in Spanish pediatric patients with IBD. There is no difference in BMD between patients with CD and UC. Lower weight and height are associated with a lower BMD; thus these data at IBD diagnosis should be considered as a risk factor for bone disease in the pediatric population.

Prevalence of low bone mineral density in Human Immunodeficiency Virus-infected patients and its correlation with other determinants

Background: The patients infected with human immunodeficiency virus (HIV) are potentially at risk of low bone mineral density (BMD). The present study was done to find out the prevalence of low BMD in HIV-infected patients and its correlation with other factors such as gender, body mass index (BMI), CD4 count, and highly active antiretroviral therapy (HAART). Methods: This was an observational cross-sectional study conducted in a tertiary care center for 1 year period. A total of 127 HIV-infected patients were evaluated for BMD by dual-energy X-ray absorptiometry (DEXA) scans at two sites lumbosacral spine and bilateral neck femur. Correlation with other factors was also studied. Results: The diagnosis of low BMD was established in 105 (82.67%) patients. Osteoporosis (44.1%) was more common than osteopenia (38.6%) at the lumbosacral spine. The mean T score of the DEXA lumbar spine and bilateral neck femur was observed to be ?2.113 and ?1.379, respectively. Males (88.73%) had low BMD than females (75%). Approximately 94.5% of subjects having BMI &lt;18 had low BMD in contrast to 80.8% among subjects having BMI &gt;18. After treatment, 47 patients had CD4 count &lt;400 and 80 &gt; 400. Forty-three patients out of 47 (91.5%) had low BMD and 62 out of 80 (77.5%) had low BMD. Conclusion: Low BMD is prevalent in HIV-infected subjects. Low BMI, persistently low CD4 count, tenofovir containing HAART regimen showed a positive correlation with low BMD. Hence, HIV infection should be considered as a risk factor for bone disease.

Osteoporosis in Primary Biliary Cholangitis: Prevalence, Impact and Management Challenges.

Primary biliary cholangitis (PBC) is a chronic, cholestatic condition associated with symptoms that directly impact the quality of life in those afflicted with the disease. In addition to pruritus and fatigue, patients with PBC may develop metabolic bone disease from reduced bone density, such as osteopenia and osteoporosis. Osteoporosis increases the risk of fractures, as well as morbidity and mortality. The prevalence of osteoporosis in PBC is expected to increase in conjunction with the rising prevalence of PBC as a whole. Timely diagnosis, prevention and management of osteoporosis are crucial in order to optimize the quality of life. There is a paucity of data evaluating the management of osteoporosis in PBC. The optimal timing for diagnosis and monitoring is not yet established and is guided by expert opinion. National guidelines recommend screening for osteoporosis at the time of diagnosis of PBC. Monitoring strategies are based on results of initial screening and individual risk factors for bone disease. Identifying reduced bone density is imperative to institute timely preventive and treatment strategies. However, treatment remains challenging as efficacious therapies are currently lacking. The data on treatment of osteoporosis in PBC are mostly extrapolated from postmenopausal osteoporosis literature. However, this data has not directly translated to useful treatment strategies for PBC-related osteoporosis, partly because of the different pathophysiological mechanisms of the two diseases. The lack of useful preventive measures and efficacious treatment strategies remains the largest pitfall that challenges the management of patients with PBC. In this review, we comprehensively outline the epidemiology, clinical implications and challenges, as well as management strategies of PBC-related osteoporosis.

Metabolic bone disease risk factors strongly contributing to long bone and rib fractures during early infancy: A population register study.

BackgroundThe aim of this study was to assess the incidence of fractures in infancy, overall and by type of fracture, its association with accidents, metabolic bone disease risk factors, and abuse diagnosis.MethodsThe design was a population-based register study in Sweden. Participants: Children born 1997–2014, 0–1 years of age diagnosed with fracture-diagnosis according to International Classification of Diseases (ICD10) were retrieved from the National Patient Register and linked to the Swedish Medical Birth Register and the Death Cause Register. Main outcome measures were fractures of the skull, long bone, clavicle and ribs, categorized by age (younger or older than 6 months), and accident or not.FindingsThe incidence of fractures during infancy was 251 per 100 000 infants (n = 4663). Major fracture localisations were long bone (44·9%), skull (31·7%), and clavicle (18·6%), while rib fractures were few (1·4%). Fall accidents were reported among 71·4%. One-third occurred during the first 6 months. Metabolic bone disease risk factors, such as maternal obesity, preterm birth, vitamin D deficiency, rickets, and calcium metabolic disturbances, had increased odds of fractures of long bones and ribs in early infancy (0–6 months): birth 32–36 weeks and long bone fracture [AOR 2·13 (95%CI 1·67–2·93)] and rib fracture [AOR 4·24 (95%CI 1·40–12·8)]. Diagnosis of vitamin D deficiency/rickets/disorders of calcium metabolism had increased odds of long bone fracture [AOR 49·5 (95%CI 18·3–134)] and rib fracture [AOR 617 (95%CI 162–2506)]. Fractures without a reported accident had higher odds of metabolic risk factors than those with reported accidents. Abuse diagnosis was registered in 105 infants, with overrepresentation of preterm births, multiple births and small-for-gestational age.InterpretationMetabolic bone disease risk factors are strongly associated with fractures of long bone and ribs in early infancy. Fracture cases with abuse diagnosis had a metabolic bone risk factor profile.

The Hidden Burden of Fractures in People Living With HIV.

ABSTRACTThe survival of people living with human immunodeficiency virus (HIV) has increased markedly since the advent of antiretroviral therapy (ART). However, other morbidities have emerged, including osteoporosis. The estimated incidence of fractures at any site in people living with HIV ranges from 0.1 per 1000 person‐years to 8.4 per 1000 person‐years: at least twice that of people without HIV. This increased risk seems to be related to HIV itself and its treatment. Risk factors for bone disease in HIV‐positive (HIV+) subjects include both classical risk factors for osteoporosis and fracture and factors linked to HIV itself, such as inflammation, reconstitution syndrome, low CD4, ART, and co‐infection with hepatitis B and C viruses. The risk of fractures in these individuals can be at least partially assessed by measurement of BMD and the Fracture Risk Assessment Tool (FRAX™). Only alendronate and zoledronic acid have been studied in HIV+ individuals; both show beneficial effects on BMD, although data on fracture reduction are not available. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Skeletal Consequences of Nephropathic Cystinosis.

Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described. We performed systematic bone and mineral evaluations of subjects with cystinosis seen at the NIH (n = 30), including history and physical examination, serum and urine biochemistries, DXA, vertebral fracture assessment, skeletal radiographs, and renal ultrasound. Additionally, histomorphometric analyses are reported on six subjects seen at the UCLA Bone and Mineral Metabolism Clinic. In NIH subjects, mean age was 20 years (range, 5 to 44 years), 60% were CKD stages G1 to G4, and 40% had a renal transplant. Mean bone mineral density (BMD) Z-scores were decreased in the femoral neck, total hip, and 1/3 radius (p < 0.05). Low bone mass at one or more sites was present in 46% of subjects. Twenty-seven percent of subjects reported one or more long bone fractures. Thirty-two percent of subjects had incidental vertebral fractures, which were unrelated to transplant status. Long-bone deformity/bowing was present in 64%; 50% had scoliosis. Diffuse osteosclerosis was present in 21% of evaluated subjects. Risk factors included CKD, phosphate wasting, hypercalciuria, secondary hyperparathyroidism, hypovitaminosis D, male hypogonadism, metabolic acidosis, and glucocorticoid/immunosuppressive therapy. Sixty-one percent of the non-transplanted subjects had ultrasonographic evidence of nephrocalcinosis or nephrolithiasis. Histomorphometric analyses showed impaired mineralization in four of six studied subjects. We conclude that skeletal deformities, decreased bone mass, and vertebral fractures are common and relevant complications of nephropathic cystinosis, even before renal transplantation. Efforts to minimize risk factors for skeletal disease include optimizing mineral metabolism and hormonal status, combined with monitoring for nephrocalcinosis/nephrolithiasis. © 2018 This article is a U.S. Government work and is in the public domain in the USA.

Inhaled glucocorticoids are associated with vertebral fractures in COPD patients.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. Vertebral fractures were identified via VFA in seven patients using ICS and in none of those not receiving glucocorticoids (p=0.02). There was a trend for an association between MMI and osteoporosis (p=0.05) and for a progressive decrease in the BMD Z-score according to the COPD severity assessed via the GOLD score (p=0.08). Vertebral fractures were not associated with osteoporosis (p=0.69) or low MMI (p=0.12). The fracture risk was not estimated by FRAX. ICS may lead to bone fragility before a significant decrease in BMD. Low muscle mass and COPD severity may contribute to bone disease.

Influence of bone mineral density measurement on fracture risk assessment tool® scores in postmenopausal Indian women.

Fracture risk assessment tool® calculations can be performed with or without addition of bone mineral density; however, the impact of this addition on fracture risk assessment tool® scores has not been studied in Indian women. Given the limited availability and high cost of bone mineral density testing in India, it is important to know the influence of bone mineral density on fracture risk assessment tool® scores in Indian women. Therefore, our aim was to assess the contribution of bone mineral density in fracture risk assessment tool® outcome in Indian women. Apparently healthy postmenopausal Indian women (n = 506), aged 40-72 years, without clinical risk factors for bone disease, were retrospectively selected, and their fracture risk assessment tool® scores calculated with and without bone mineral density were compared. Based on WHO criteria, 30% women were osteoporotic, 42.9% were osteopenic and 27.1% had normal bone mineral density. Fracture risk assessment tool® scores for risk of both major osteoporotic fracture and hip fracture significantly increased on including bone mineral density (P < 0.0001). When criteria of National Osteoporosis Foundation, US was applied number of participants eligible for medical therapy increased upon inclusion of bone mineral density, (for major osteoporotic fracture risk number of women eligible without bone mineral density was 0 and with bone mineral density was 1, P > 0.05, whereas, for hip fracture risk number of women eligible without bone mineral density was 2 and with bone mineral density was 17, P < 0.0001). Until the establishment of country-specific medication intervention thresholds, bone mineral density should be included while calculating fracture risk assessment tool® scores in Indian women.

Osteoporosis in Liver Transplant Recipients: Defining Incidence and Risk Factors

Introduction: Osteoporosis is common disorder among patients with liver transplantation (LT). However, specific risk factors for bone disease in this population have not been fully elucidated. In general population, research has linked hypertension to osteoporosis, but data linking hypertension and osteoporosis in LT recipients is scarce. Studies have shown that in kidney transplant recipients, high levels of Tacrolimus (TAC) is associated with risk of bone loss, but data on association between use of TAC and bone disease in LT recipients is scarce. We aimed to define the incidence and risk factors associated with bone disease, among our LT recipients. Methods: We conducted a retrospective review of LT recipients from our prospective database with the ICD-9 code V42.7 for “liver replaced by transplant”. The study population included patients who had received LT at our institution between 2010 and 2013. We recorded recipients' DEXA scan findings, age, sex, height, weight, previous medical conditions, drug use, alcohol consumption, and medications. In addition, vitamin D levels, CBC, comprehensive metabolic panel, and lipid panel were recorded before and after LT and at last follow up. All data was recorded in Microsoft Excel and analyzed using mean and SD. Results: Of the 46 recipients identified, 24 had DEXA scans; sixteen (67%) had osteoporosis and 29% had osteopenia, only one had a normal study. The average age at diagnosis was 58 ± 9 years with a male to female ratio of 11:13. The average BMI was 28.0 ± 5.5 kg/m2. Hepatitis C was the most common etiology for transplant (78%). Eighteen (78%) had hypertension and 17 (74%) were diabetic. Seventeen patients (71%) had a history of tobacco use. All recipients (100%) had at least one of these three afore mentioned risk factors. The median vitamin D level was 25 ng/mL and 29 ng/mL in recipients with osteoporosis and osteopenia respectively (P=0.41). The mean corrected calcium level was 9.5 ± 0.79 mg/dL and 9.2 ± 0.75 mg/dL. Sixteen recipients (70%) were on Tacrolimus, which was the most common medication in this population. Conclusion: We had a high incidence of osteoporosis/osteopenia (96%) in our cohort of LT recipients. Bone disease is significant comorbidity in LT recipients. All recipients had either hypertension, diabetes, or a history of tobacco use, and 70% were on Tacrolimus. Prospective studies are required to better define the relation between these risk factors and bone disease in this unique population.

Reversible bone lesions induced by tenofovir disoproxil fumarate

Metabolic bone disease is increasingly common in HIV-infected patients on antiretroviral therapy (ART) [1]. Manifestations of ART-induced bone disease include low bone mineral density, increased bone turnover, osteopenia, osteoporosis, and increased fracture risk [2–4]. To our knowledge, reversible tenofovir disoproxil fumarate (TDF)-induced bone lesions have not been described. We describe a patient who developed diffuse foci of increased bone turnover on a TDF-containing regimen and which resolved upon discontinuation of TDF. A 33-year-old Caucasian woman with HIV had multiple risk factors for metabolic bone disease including low BMI, Caucasian race, and tobacco use. A protease inhibitor-containing regimen was initiated and eventually included TDF, which continued unabated for 74 months. Severe lower-extremity pain began approximately 36 months after TDF was added, occurred with movement, and limited activities of daily living (ADL). Eventually, generalized pain extended to the wrists, upper arms, and thorax, and fluctuated in intensity for several months. At 74 months, pain was reported to be excruciating with significant overall impairment of ADL. Chemistries and serum markers for bone disease including vitamin D, parathyroid hormone, and calcium were within normal limits, with the exception of alkaline phosphatase and liver transaminases, each of which was greater than two and three times the upper limit of normal, respectively. Serum creatinine and blood urea nitrogen were normal. All antiretrovirals were discontinued due to severe bone pain. A technetium bone scan revealed multiple foci of increased activity in distal tibiae, bilateral calcaneus bones, multiple costovertebral junctions and ribs, sternum, sacroiliac joints, and right iliac and superior pubic ramus (Fig. 1). Shortly after these findings, the same protease inhibitor-containing regimen, without TDF, was resumed. The patient reported significant improvement in pain and function 3 months later, and a bone scan 11 months after stopping TDF was normal. Additionally, alkaline phosphatase declined shortly after TDF was discontinued and normalized 12 months later.Fig. 1: Technetium bone scan.In conclusion, reversible bone lesions detected by technetium bone scan present a unique finding and a likely manifestation of TDF-induced metabolic bone disease. In our patient, imaging abnormalities occurred after greater than 6 years of continued TDF use, and resolved after 11 months of TDF-sparing ART, whereas other risk factors for bone disease, including protease inhibitor use, remained constant. A bone scan may be useful for discriminating pain caused by metabolic bone disease on long-term TDF from other types of chronic pain. Acknowledgements Conflicts of interest Financial support: No financial support was received for the manuscript. Disclaimers: There are no conflicts of interest for Staci M. Lockhart or Douglas A. Drevets.

Treatment of Epilepsy to Optimize Bone Health

When treating a person with epilepsy, one must consider many factors in addition to the obvious need to treat the seizures. Both epilepsy itself and treatment with antiepileptic drugs (AEDs) subject one to numerous potential secondary long-term health concerns. Poor bone health is one of these concerns. Studies suggest that persons with epilepsy treated with AEDs have an increased risk of fracture, low bone mineral density (BMD), and abnormalities in bone metabolism. Multiple factors likely contribute to the increased risk. Falls during generalized tonic-clonic seizures, secondary effects of AEDs on balance, inactivity, low BMD, reduced calcium intake, reduced active vitamin D metabolites, and a genetic predisposition to low BMD may all contribute. Studies suggest a differential influence of AEDs. Phenytoin, phenobarbital, and primidone are most consistently associated with a negative impact on bone. Carbamazepine and valproate may also result in bone abnormalities, but data are mixed. Current studies suggest that lamotrigine has limited (if any) effect, but again, data are inconsistent. Other AEDs have received limited study. Screening for poor bone health includes serologic testing of vitamin D metabolites (notably 25-hydroxyvitamin D) as well as BMD testing using dual energy x-ray absorptiometry. Optimizing intake of calcium and vitamin D is important for all persons with epilepsy treated with AEDs. Although many treatments for low BMD are available, these agents have not been studied in persons with epilepsy treated with AEDs. Overall, physicians treating persons with epilepsy must consider the potential effect of having epilepsy and its main treatment, AED therapy, on bone health. For patients in whom bone health is a particular concern (eg, those with diagnosed bone disease or with significant risk factors for bone disease, including glucocorticosteroid use), it is best to avoid AEDs known to negatively affect bone. In addition, practitioners should work with other treating physicians to optimize bone health in these patients.

1007 Osteoporosis and Bone Disorders in Paediatric Renal Transplantation Recipients

Decreased bone mineral density (BMD) is common in renal transplantation recipients (RTR). Osteoporosis has a major role in morbidity in these patients. Risk factors for decreased bone mass include underlying renal disease, nutritional deficits, decreased physical activity, inflammation and immunosuppressive therapy.We assessed the prevalence of osteoporosis and risk factors for bone disease in patients with at least 6 moths post renal transplantation. The patients underwent clinical and laboratory evaluation, dualenergy X- ray absorptiometry (DXA) for BMD in lumbar spine (LS) and femoral neck. Low bone mineral density was defined by lumbar spine Z-scores less than or equal to -2 on DXA using the equipment-specific age, sex- and ethnicity - adjusted.The study included 24 subjects who were between 7 and 18 years of age. The incidence of osteoporosis was 25% (6/24). We found 6 patients, all teenagers, 4/6 boys. Other bone disorders were 1 child with bone fracture, 1 genu valgum submitted to surgery and 1 femoral head avascular necrosis, but without osteoporosis diagnosed.Four patients had PTH value >100 ng/liter, one of these with LS Z-score less than (-2). All were on triple drug immunosuppression with prednisolone, tacrolimus and mycophenolate mofetilIn conclusion, although DXA has several limitations it remains a good method for non-invasive and reproducible BMD assessment in children and young adults. Osteoporosis is a frequent complication and requires detection and treatment to reduce morbidity. The prevention of bone disorders is very important.

Bone Disease in HIV Infection: A Practical Review and Recommendations for HIV Care Providers

Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected subjects. Initiation of antiretroviral therapy is associated with a 2%-6% decrease in BMD over the first 2 years, a decrease that is similar in magnitude to that sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review, we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ⩾50 years of age. We also discuss the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of bone disease, while outlining the caveats and gaps in our knowledge.

Vitamin D and Cardiovascular Disease: A Novel Agent for Reducing Cardiovascular Risk?

Vitamin D deficiency is a well-established risk factor for bone disease. Emerging data suggest a pleiotropic role of this agent in a variety of functions in humans. Epidemiological studies indicate an inverse association between vitamin D deficiency and the prevalence of cardiovascular disease (CVD), as well as individual cardiometabolic risk factors, such as hypertension, diabetes, dyslipidemia and the metabolic syndrome. Moreover, vitamin D deficiency has been implicated in the atherosclerotic process. This review considers current data regarding the role of vitamin D deficiency in the development of CVD and addresses the effect of supplementation on cardiovascular outcomes.

Basic and clinical aspects of osteoporosis in inflammatory bowel disease

Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease (IBD) has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors (VDRs) and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B (RANK), RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography (QCT), radiographic absorptiometry, and ultrasound. DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, while new emergent therapies such as calcitonin and teriparatide among others remain to be assessed.

Bone Diseases Associated with Human Immunodeficiency Virus Infection: Pathogenesis, Risk Factors and Clinical Management

Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.