Development Of Metabolic Bone Disease Research Articles

Estrogen deficiency induces bone loss through the gut microbiota

Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in the development of metabolic bone disease. Here, we show that ovariectomized mice had high levels of lipopolysaccharide in serum and gut microbiota dysbiosis through increases in luminal Firmicutes:Bacteroidetes ratio. We depleted the GM through antibiotic treatment and observed improvements in bone mass, bone microstructure, and bone strength in ovariectomized mice. Conversely, transplantation of GM adapted to ovariectomy induced bone loss. However, GM depletion reversed ovariectomy-induced gene expression in the tibia and increased periosteal bone formation. Furthermore, bioinformatics analysis revealed that the G-protein-coupled bile acid receptor (TGR5) and systemic inflammatory factors play key roles in bone metabolism. Silencing TGR5 expression through small interfering RNA (siRNA) in the local tibia and knockout of TGR5 attenuated the effects of GM depletion in ovariectomized mice, confirming these findings. Thus, this study highlights the critical role of the GM in inducing bone loss in ovariectomized mice and suggests that targeting TGR5 within the GM may have therapeutic potential for postmenopausal osteoporosis.

Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study

BackgroundCaffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss can promote the development of metabolic bone disease (MBD) in preterm neonates. This study aimed to evaluate the effect of the caffeine regimen on the development of osteopenia of prematurity (OOP), using serum alkaline phosphatase (serum-ALP) concentrations as a surrogate marker at the 4th week of life.MethodsThis retrospective cohort study was conducted including neonates of < 32 weeks gestational age (GA) and birth weight < 1500 g, admitted to NICU from April-2017 to December-2018 and received caffeine therapy till 28 days of life for AOP. Based on serum-ALP levels, formed the high and low-ALP groups. Neonatal characteristics, caffeine regimen, risk factors for OOP, including duration of parenteral nutrition (PN), exposure to medicines associated with MBD, and intake of essential vitamins and minerals, were compared in both groups. Predictors of OOP were analyzed through logistic regression.ResultsFrom the total of 268 participants, 52 (19%) developed OOP, mostly female (61.5%). In the high ALP group, the serum-ALP levels were significantly higher than in the low-ALP group (725.0 ± 143.8 vs 273.6 ± 55.0 units/L, p < 0.001). The high-ALP group received significantly (p < 0.001) higher daily and cumulative caffeine doses and were associated with a higher likelihood of developing OOP in this study cohort [cumulative dose (mg) (AOR = 1.082 95% CI 1.011 to 1.157) and daily dose (mg/kg/day) (AOR = 2.892 95% CI 1.392 to 6.007)]. Smaller GA was found directly related to OOP. Among the other medical risk factors, phosphorus intake was significantly low in the high-ALP group. No, significant relationship between duration of PN and use of steroids and diuretics, and intake of vitamins and minerals were identified.ConclusionThe daily and cumulative doses of caffeine and smaller GA are associated with the development of OOP in this study cohort. Clinical randomized control studies are needed to validate the outcomes and determine the range of safest and most effective caffeine doses for treating AOP in preterm neonates.

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

The Effects of Different Parenteral Nutrition Lipid Formulations on Clinical and Laboratory Endpoints in Patients Receiving Home Parenteral Nutrition: A Systematic Review

Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes.1 Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life2 but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood.

1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation.

Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

The effects of different parenteral nutrition lipid formulations on clinical and laboratory endpoints in patients receiving home parenteral nutrition: A systematic review

Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints. A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies. Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n=5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive+/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles. Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive+/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis.

Bone Mineral Composition Among Long-Term Parenteral Nutrition Patients: Postmortem Assessment of Calcium, Phosphorus, Magnesium, and Select Trace Elements.

Patients receiving long-term parenteral nutrition (PN) treatment are at risk of developing metabolic bone diseases (MBDs). The bone compartment serves as a repository for a range of metal(loid)s that are administered intravenously to patients via PN solutions. Thus, the mineral composition of patient bones may be linked to the development of MBDs in this group. We measured 12 elements in bone samples obtained post mortem from 7 long-term (2-21 years) PN patients and 18 control bones obtained from hip/knee replacement surgery. The samples were cleaned, digested, and subsequently analyzed using a method based on inductively coupled plasma tandem mass spectrometry. Compared with the control group, bones obtained from PN patients were significantly (P<0.05) depleted in calcium (Ca), phosphorus (P), magnesium (Mg), chromium, and strontium and enriched in manganese (Mn), zinc, barium, cadmium (Cd), and uranium (U). No differences were observed for cobalt or lead. Depletion of major components of bone mineral (Ca, P, and Mg) and enrichment in known toxicants (Cd, Mn, U) are concerns for PN patients.

Metabolic Disturbance in Women with Polycystic Ovary Syndrome and its Impact on Bone Turnover

Background: Insulin resistance and abdominal obesity are main characteristics of polycystic ovary syndrome, women with this syndrome at high risk for prolong term metabolic disorders. Obesity, insulin resistance, and hyperinsulinemia affect the hormones that control calcium homeostasis. Lower levels of serum vitamin D and higher levels of serum parathyroid hormone were found in women with polycystic ovary syndrome. However, high levels of parathyroid hormone can reduce bone mineral density and increase bone turnover. Objectives: The present study aimed to measure the parameters of bone metabolism including parathyroid hormone, calcium, and phosphorous in serum of women with polycystic ovary syndrome and compare their levels with healthy controls. Also, investigate the possible impact of metabolic alterations in polycystic ovary syndrome on bone turnover. Material and Method: This case-control study included 82 women from 20 to 37 years of age. All women were selected from Infertility Center in Baghdad Teaching Hospital during the period from 1 June 2019 to 30 August 2019. Women were divided into two groups: group (1) involved 42 women with polycystic ovary syndrome and group (2) involved 40 healthy women (act as controls). Each Serum specimen was analyzed for the measuring of parathyroid hormone, calcium, phosphorous, fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance (HOMA-IR). Results: Significantly higher serum levels of parathyroid hormone, calcium,fasting insulin, and fasting glucose with lower levels of serum phosphorous in women with polycystic ovary syndrome as compared with healthy women. In addition, significant positive correlation was found between serum parathyroid hormone and waist circumference (r=0.609, p=0.00001) as well as between serum parathyroid hormone and HOMA-IR (r= 0.781, p=0.00001). Conclusion: The metabolic disturbance found in polycystic ovary syndrome tend to support the relation between this syndrome and defective bone metabolism. High prevalence of obesity and high levels of insulin, HOMA-IR, and parathyroid hormone were found in women with this syndrome which in turn affect bone turn over. Thus, women with polycystic ovary syndrome are at risk for the development of metabolic bone disease.

Measurement of Serum Chemerin and Deoxypyridinoline Levels in Iraqi ‎Osteoporotic ‎Postmenopausal Women with and without Metabolic Syn-drome

Metabolic syndrome is a cluster of medical conditions composed of ‎abdominal obesity, ‎hyperglycemia, hypertension, and lipid abnormalities, in which ‎each can affect bone in ‎different ways. We examine ‎the association between metabolic syndrome and metabolic bone disease ‎‎(osteoporosis) by ‎measuring adipose tissue marker (chemerin) and bone resorption ‎marker ‎‎(deoxypyridinoline) in ‎the serum of osteoporotic postmenopausal women with ‎and without ‎metabolic syndrome. ‎ A case-control study included 112 postmenopausal women from 51 to 67 years of ‎age. ‎Women were ‎selected from Osteoporosis Clinic- Al Yarmouk Teaching ‎Hospital and were ‎divided into two ‎groups: group (1)- patients group included 57 ‎postmenopausal women with ‎osteoporosis (35 ‎osteoporotic women with metabolic ‎syndrome and 22 osteoporotic women ‎without metabolic ‎syndrome) and group ‎‎(2)-control group included 55 postmenopausal women ‎without ‎osteoporosis and ‎metabolic syndrome. A serum sample was taken from each woman and ‎analysed ‎for ‎assessing chemerin, deoxypyridinoline, fasting serum glucose, and lipid profile. We found ‎a significant increase (p-value&lt;0.001) in the mean value of serum chemerin ‎and ‎deoxypyridinoline ‎levels in patients compared to controls. ‎In ‎conclusion, chemerin is an adipose tissue marker associated with metabolic syndrome ‎and ‎may ‎have an impact on bone turn over and development of metabolic bone ‎disease ‎which ‎enhanced by the strong positive correlation between chemerin and bone ‎resorption ‎marker ‎‎(deoxypyridinoline).

Gut microbiota, probiotics, prebiotics and bone health: a review

Gut microbiota is widely accepted to play a crucial role to host health via the regulation of many physiological functions, including metabolism, nutrition, pathogen resistance, and immune function. Over the last decades, accumulating evidence has also pinpointed a role for gut microbiota on bone metabolism and the development of metabolic bone diseases, such as osteoporosis. Emerging evidence suggests the potential of gut microbiota as a promising target for bone health management. In this contribution, we have examined the available literature to understand the role of gut microbiota on bone metabolism as well as the underlying mechanisms. Furthermore, the application and effectiveness of using probiotics/prebiotics as means to modify gut microbiota and bone health are discussed. In this relation, animal studies and human trails suggest that alternation of gut microbiota composition can exert the activity of bone metabolism and therefore lead to the change of bone quality. It is believed that gut microbiota regulates bone metabolism via host immune system, endocrine system and mineral absorption. Supplementation with probiotics and prebiotics to both animals and humans has demonstrated promising, but sometimes conflicting results, on bone health. Thus, future research is expected to reveal the influence of the variations in age, gender, dose, delivery method, and treatment duration, among others on the probiotics/prebiotics-targeted bone diseases treatment.

Evaluation of the effects of gastrectomy on the development of metabolic bone disease

BackgroundMetabolic bone disease after gastrectomy is one of the complications leading to deterioration in quality of life. The exact mechanism of the metabolic bone disease remains unclear. To clarify the cause of metabolic bone disease after gastrectomy, we evaluated the associations between the method of gastrectomy and the development of metabolic bone disease in a rat model. MethodsRats were assigned to four groups as follows: (1) sham operation (control group); (2) resection of the glandular stomach with Billroth I reconstruction (RGBI group); (3) Roux-en-Y anastomosis preserving the secretory function of the whole stomach (PSRY group); and (4) total gastrectomy with Roux-en-Y reconstruction (TGRY group). In all groups, body weight, serum biochemistry (total protein, albumin, calcium, phosphorus, tartrate-resistant acid phosphatase, and bone alkaline phosphatase), bone density, and bone breaking strength were measured. ResultsBody weights and serum calcium levels were significantly lower in the three operation groups compared with the control group. Bone density was significantly lower in the PSRY and TGRY groups compared with the control group. Bone breaking strength was significantly lower in the three operation groups compared with the control group. ConclusionsSurgical methods led to metabolic bone disease. However, exclusion of the duodenum from food passage had major influence to reduction in bone density and breaking strength. A stomach-preserving procedure and physiological reconstruction which enable food passage through duodenum and proximal jejunum contribute to mitigation of metabolic bone disease.

Clinical correlations between chronic hepatitis C infection and decreasing bone mass density after treatment with interferon-alpha

ObjectiveTo compare the bone mass density in chronic hepatitis patients before and after interferon-α treatment. MethodsA total of 70 patients with chronic hepatitis C were treated with interferon-α and were evaluated. The treatment dosage was three million IU three times a week for one year. All the patients underwent bone mass density detection at lumbar spine and femoral neck before and after the interferon-α treatment. All the necessary information such as age, sex, and laboratory test, history of occurrence of fractures, lifestyle, and menopause status was collected by interviewers face-to-face from participants at the research visit. Smoking was categorized by whether participants were nonsmokers or smokers. Menopause was designated if there had been complete cessation of menses for more than 12 months. All statistical analyses were performed by SPSS version 14 (SPSS, Inc., Chicago, IL, USA). ResultsAmong 70 patients, 52% were male, 48% were female and the mean age was (57.0 ± 9.6) years (range: 24–79). Twenty-nine percent of the patients had a history of smoking. The mean body mass index was (24.4 ± 3.6) kg/m2 (range: 18.4–35.3). Of the 70 cases, 21 had high fibrosis-4. The prevalence of overall fracture history was 2.9% (two patients). ConclusionsChronic hepatitis C virus infection did increase the risk of development of metabolic bone disease in this cohort. Indeed, greater reduction of bone mass density occurs in advanced liver fibrosis. The bone loss in earlier stages of chronic hepatitis C infection is likely to result from increased bone reduction rather than decreased bone formation. Overall, these observations suggest an important role for chronic hepatitis C virus infection in increased bone turnover in osteodystrophy pathogenesis.

Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants.

Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures.

Pediatric intestinal failure: Predictors of metabolic bone disease

PurposeThe purpose of this study was to identify risk factors for the development of metabolic bone disease (MBD) in pediatric intestinal failure (IF). MethodsA retrospective single-center study of 36 pediatric IF patients who were screened for MBD was performed. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Simple regression analysis was initially performed to screen predictors, followed by multivariate step-wise linear regression analysis to identify risk factors of MBD. ResultsMean lumbar spine BMD Z-score was −1.16±1.32, and 50.0% of patients had a BMD Z-score less than −1.0. Deficiency of 25-hydroxyvitamin-D (25-OHD <30ng/ml) was present in the 63.8% of patients, while 25.0% had hyperparathyroidism (intact parathyroid hormone (PTH)>55pg/ml). Seven patients (19.4%) had bone pain, of which 4 (11.1%) suffered a pathologic fracture. Using multivariate analysis, parenteral nutrition (PN) duration predicted decreased BMD (B=−0.132, p=0.006). Serum 25-OHD nonsignificantly correlated with BMD Z-score (B=0.024, p=0.092). Interestingly, repeat DXA after increasing vitamin D supplementation showed no improvement in BMD Z-score (−1.18±1.49 vs −1.36±1.47, p=0.199). ConclusionsPediatric IF is associated with a significant risk of MBD, which is predicted by the duration of PN-dependence. These findings underscore the importance of BMD monitoring. Better therapies for treating IF-associated MBD are needed.

Metabolic bone disease following urinary diversion in adults.

Urinary diversions are created following radical cystectomy or for the palliation of recalcitrant lower urinary tract symptoms. Chronic metabolic acidosis, one of the several long-term complications associated with urinary diversion, has been shown to lead to metabolic bone disease if untreated. The incidence of chronic acidosis can be influenced by several factors, including type and length of bowel segment utilized, renal function, and type of urinary diversion. The observed rate of acidosis has been noted to be high, particularly in patients undergoing continent ileal neobladders using long bowel segments. Results from the five selected case series evaluating the association between urinary diversion and development of metabolic bone disease are inconsistent, but the majority report a low incidence of bone disease, ranging from 0 to 15%. In order to decrease the risk of developing metabolic bone disease and the other associated disorders, attention to the diagnosis of acidosis postoperatively, along with preventive therapy, is crucial. Treatment of acidosis secondary to urinary diversion may be accomplished in the long term with oral alkalizing agents. Although there is no clear relationship between urinary diversion and the future development of metabolic bone disease, diagnosis and treatment of postoperative acidosis are recommended.

Bones, Fractures, Antiretroviral Therapy and HIV.

The course of HIV infection has been dramatically transformed by the success of antiretroviral therapy from a universally fatal infection to a manageable chronic disease. With these advances in HIV disease management, age-related comorbidities, including metabolic bone disease, have become more prominent in the routine care of persons living with HIV infection. Recent data have highlighted the role of HIV infection, initiation of antiretroviral therapy, and hepatitis C virus coinfection in bone mineral density loss and fracture incidence. Additionally, the underlying mechanism for the development of metabolic bone disease in the setting of HIV infection has received considerable attention. This review highlights recently published and presented data and synthesizes the current state of the field. These data highlight the need for proactive prevention for fragility fractures.

METABOLIC BONE DISEASE IN JUVENILE KOALAS (PHASCOLARTCOS CINEREUS)

Due to climate restrictions in parts of North America and Europe, koalas (Phascolarctos cinereus) are housed indoors. Koala young (joeys) raised indoors are susceptible to the development of metabolic bone disease (MBD) due to a lack of exposure to natural ultraviolet light to themselves and their female parents (dams). In this retrospective study, radiographs from 27 koala joeys born at four zoos in North America and two zoos in Europe were evaluated for signs of MBD. Eight of the joeys were radiographically diagnosed with MBD and four additional joeys were considered suspect MBD cases; in two joeys absence or presence of MBD could not be determined. All joeys had mild to severe hip and shoulder dysplasia. There were significant associations between a lack of exposure to UV light and MBD development and between MBD and the degree of severity of hip and shoulder dysplasia. It is recommended to house breeding female koalas and their joeys outdoors whenever possible.

SERUM VITAMIN D LEVELS IN FREE-RANGING KOALAS (PHASCOLARCTOS CINEREUS)

Due to climatic conditions in Northern America and Europe, koalas (Phascolarctos cinereus) are often housed indoors. Koala joeys raised in these environments are susceptible to the development of metabolic bone disease due to a lack of exposure to solar ultraviolet radiation to themselves and their dam. As an initial step toward describing vitamin D sufficiency and adequately measuring responses to supplementation, vitamin D values were calculated by using serum collected from 20 free-ranging koalas on St. Bees Island, Queensland, Australia. Vitamin D values ranged from 8.1 to 30.4 pg/ml (18.4 +/- 5.5 pg/ml) for 1, 25-hydroxyvitamin D, and from 1 to 14 nM/L (7.4 +/- 3.0 nM/L) for 25-hydroxyvitamin D. These koala serum vitamin D values are unusually low when compared with eutherian mammals. Although this study was limited in numbers and in the geographically range of the koalas sampled, it does suggest that the koala's requirement for vitamin D is low. Therefore, supplementation to prevent disease may be relatively easy to achieve because low doses will likely meet requirements. Caution should be taken to avoid intoxication if supplementing vitamin D in koalas.

Nutritional deficiencies after bariatric surgery

Lifestyle intervention programmes often produce insufficient weight loss and poor weight loss maintenance. As a result, an increasing number of patients with obesity and related comorbidities undergo bariatric surgery, which includes approaches such as the adjustable gastric band or the 'divided' Roux-en-Y gastric bypass (RYGB). This Review summarizes the current knowledge on nutrient deficiencies that can develop after bariatric surgery and highlights follow-up and treatment options for bariatric surgery patients who develop a micronutrient deficiency. The major macronutrient deficiency after bariatric surgery is protein malnutrition. Deficiencies in micronutrients, which include trace elements, essential minerals, and water-soluble and fat-soluble vitamins, are common before bariatric surgery and often persist postoperatively, despite universal recommendations on multivitamin and mineral supplements. Other disorders, including small intestinal bacterial overgrowth, can promote micronutrient deficiencies, especially in patients with diabetes mellitus. Recognition of the clinical presentations of micronutrient deficiencies is important, both to enable early intervention and to minimize long-term adverse effects. A major clinical concern is the relationship between vitamin D deficiency and the development of metabolic bone diseases, such as osteoporosis or osteomalacia; metabolic bone diseases may explain the increased risk of hip fracture in patients after RYGB. Further studies are required to determine the optimal levels of nutrient supplementation and whether postoperative laboratory monitoring effectively detects nutrient deficiencies. In the absence of such data, clinicians should inquire about and treat symptoms that suggest nutrient deficiencies.

Vitamin D status in a sunny country: Where has the sun gone?

Hypovitaminosis D [serum 25 vitamin D<30 ng/ml] is related to the development of metabolic bone disease and greater risk of chronic illnesses. However, it is frequently under-diagnosed, mainly in countries where UV radiation is abundant. We prospectively determined the prevalence and the predictors of serum 25 vitamin D (s25(OH)D) in a healthy Brazilian population after the winter and after the summer. 603 (118M and 485F) healthy Brazilian volunteers aged 18-90 years from a universitary hospital were selected after the winter of 2006. From the initial sample, 209 volunteers (31M and 178F) accepted to participate in a second health check after the subsequent summer. After the winter, median s25(OH)D was 21.4 ng/mL and 77.4% of the population presented hypovitaminosis D. s25(OH)D was significantly related to age, BMI, PTH and race. In multivariate linear regression analysis, s25(OH)D was significantly and independently dependent on age, glycemia and skin color. Significant increase in s25(OH)D was verified after summer [10.6 (3.7-19.3 ng/ml); p<0.001] and this improvement was dependent on age. We also observed a significant decrease in hyperparathyroidism prevalence (20.8% vs. 4.9%; P<0.0001). In São Paulo, at the end of winter, we observed a high prevalence of hypovitaminosis D and secondary hyperparathyroidism in healthy adults. s25(OH)D was dependent on age and skin color. After summer, we observed a decrease in the prevalence of hypovitaminosis D. This unexpected finding emphasizes the need for a strong recommendation to monitor s25(OH)D, even in a sunny country such as Brazil.