Balancing Altered Calcium Metabolism with Bone Health in Sarcoidosis.

Abnormal calcium metabolism in sarcoidosis patients can lead to hypercalcemia, hypercalciuria, and kidney stones. Hypercalcemia in sarcoidosis is usually due to increased activity of 1α-hydroxylase in macrophages of pulmonary granulomata, resulting in low levels of 25-hydroxyvitamin D and high levels of calcitriol. Vitamin D supplementation may be dangerous for some sarcoidosis patients and is recommended only for those with decreased 25-hydroxyvitamin D and reduced or normal calcitriol level. Diagnosis, treatment of osteoporosis, and maintenance of bone health are complex issues for sarcoidosis patients. An approach to diagnosis and treatment of bone fragility is presented.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PURPOSE OF REVIEW: Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. RECENT FINDINGS: Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. SUMMARY: Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease.

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Bone mineralization disorders as a complication of anorexia nervosa - etiology, prevalence, course and treatment. / Zaburzenia mineralizacji kosci jako powiklanie jadlowstretu psychicznego - etiologia, rozpowszechnienie, przebieg i leczenie.

Anorexia nervosa (AN) most often has its onset in adolescence, which is a crucial period to achieve peak bone mass. The hormonal abnormalities (hypoestrogenism, hypercortisolism, decreased secretion of dehydroepiandrosterone, testosterone, insulin-like growth factor) and malnutrition are associated with profound bone mineralization disorders. Densitomertic bone mineral density (BMD) values for osteopenia and osteoporosis were found respectively in 35-98% and 13-50% of women with AN. Prospective studies indicate a further decline in BMD at the beginning of treatment and a crucial importance of weight gain and return of spontaneous menses for its growth. Due to frequent chronic and relapsing course of AN densitometric assessment of BMD is recommended in all patients with AN and amenorrhea lasting around twelve months. In order to establish standards for the treatment of osteoporosis in AN, studies on pharmacological treatment are conducted. There are promising results indicating the improvement in BMD after treatment with physiologic oestrogen replacement treatment and sequential administration of medroxyprogesterone in teenage girls and bisphosphonates in adult women. Supplementation of vitamin D and adequate consumption of calcium from diet are recommended. Further studies on the effectiveness of long-term treatment of osteoporosis with regard to the possibility of increase in BMD and reducing the risk of osteoporotic fractures are needed.

Chronic Kidney Disease-Mineral Bone Disorder in the Elderly Peritoneal Dialysis Patient.

PURPOSE: The purpose of this paper was to review the literature concerning the treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) in the elderly peritoneal dialysis (PD) patient. RESULTS: Chronic kidney disease-mineral bone disorder is a major problem in the elderly PD patient, with its associated increased fracture risk, vascular calcification, and accelerated mortality fracture risk. Peritoneal dialysis, however, bears a lower risk than hemodialysis (HD). The approach to CKD-MBD prophylaxis and treatment in the elderly PD patient is similar to other CKD patients, with some important differences. Avoidance of hypercalcemia, hyperphosphatemia, and hyperparathyroidism is important, as in other CKD groups, and is generally easier to attain. Calcium-free phosphate binders are recommended for normocalcemic and hypercalcemic patients. Normalization of vitamin D levels to > 75 nmol/L (> 30 pg/L) and low-dose active vitamin D therapy is recommended for all patients. Hyperparathryoidism is to be avoided by using active vitamin D and cinacalcet. Particular attention should be paid to treating protein malnutrition. Fracture prophylaxis (exercise, use of walkers, dwelling modifications) are important. Hypomagnesemia is common in PD and can be treated with magnesium supplements. Vitamin K deficiency is also common and has been identified as a cause of vascular calcification. Accordingly, warfarin treatment for this age group is problematic. CONCLUSION: While treatment principles are similar to other dialysis patient groups, physicians should be aware of the special problems of the elderly group.

Bone mineral density loss after combat-related lower extremity amputation.

OBJECTIVES: Determine the incidence, severity, and associated risk factors for the development of low bone mineral density (BMD) after combat-related lower extremity amputation. DESIGN: Retrospective case-control comparison. SETTING: Tertiary care military treatment facility. PATIENTS/PARTICIPANTS: One hundred fifty-six lower extremity amputees, representing 182 amputations (121 unilateral, 35 bilateral). INTERVENTION: All patients underwent dual energy x-ray absorptiometry scanning during the treatment period. MAIN OUTCOME MEASUREMENTS: The Z score was the main outcome measure. We identified all patients with low BMD (Z < -1.0) and conducted multivariate analysis to identify significant risk factors for low BMD development. RESULTS: The observed rate of low BMD was 42%. The average Z score was -0.6 ± 1.1 among unilateral amputations and -1.2 ± 1.0 among bilateral amputations (P = 0.005). Risk factors for the development of low BMD were prolonged time to first ambulation [odds ratio (OR) = 1.39; 95% confidence interval (CI): 1.003-1.93; P = 0.048], prolonged time to dual energy x-ray absorptiometry (OR = 1.10; 95% CI: 1.02-1.18; P = 0.009), and more proximal amputation level (OR = 7.27; 95% CI: 3.21-16.49; P < 0.001). Among unilateral amputees, we detected a significant difference in the BMD of the intact and amputated limbs (-1.0; 95% CI: -1.1 to -0.8; P < 0.001). CONCLUSIONS: Proximal amputation level and delayed ambulation demonstrated a significant relationship with low BMD after traumatic and trauma-related amputation. We conclude that transfemoral amputees are at greater risk of BMD loss and that disuse atrophy is a primary factor in the development of low BMD. Prevention should focus on early and aggressive weight bearing rehabilitation and assessing levels and appropriately supplementing calcium and vitamin D.

Phosphate binders in moderate chronic kidney disease: where do we stand?

Phosphate levels are strikingly associated with poor outcomes in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Numerous epidemiological studies have repeatedly documented a worrisome link between serum phosphorus and adverse outcome in CKD stages 3 and 4. Notably, some but not all series suggest that the risk is significantly increased even for serum levels within the reference range of normality for serum phosphorus. The use of phosphate binders as a tool for controlling hyperphosphatemia has also been associated in observational studies with a better survival both in CKD and ESRD. However, no randomized clinical trial (RCT) has ever tested the impact of phosphate-lowering interventions (i.e., phosphate binder or nutritional intervention) on hard outcomes. Furthermore, a recent RCT seems to caution against the indiscriminate use of phosphate binders in CKD patients not receiving maintenance dialysis. Considering the clinical sequelae associated with phosphate overload in CKD, phosphate-lowering therapy is perceived as crucial and safe to prevent chronic kidney disease-mineral bone disorder (CKD-MBD). However, when to start in the course of CKD, how to monitor and whether to choose a calcium-based or a calcium-free phosphate binder are still subject to debate. Further research is deemed necessary to elucidate whether early treatment with phosphate binders is safe and may attenuate the CKD-MBD progression through phosphate load reduction.

A study to evaluate the cause of bone demineralization in gynecological cancer survivors.

BACKGROUND: An association between treatment for gynecological cancers and risk of osteoporosis has never been formally evaluated. Women treated for these cancers are now living longer than ever before, and prevention of treatment-induced morbidities is important. We aimed to distinguish, in gynecological cancer survivors, whether cancer therapy has additional detrimental effects on bone health above those attributable to hormone withdrawal. METHODS: We performed a retrospective cross-sectional analysis of dual energy x-ray absorptiometry (DEXA) scan results from 105 women; 64 had undergone bilateral salpingo-oophorectomy (BSO) followed by chemotherapy or radiotherapy for gynecological malignancies, and 41 age-matched women had undergone BSO for benign etiologies. All were premenopausal prior to surgery. RESULTS: The median age at DEXA scan for the cancer group was 42 years, and 66% had received hormonal replacement therapy (HRT) following their cancer treatment. For the benign group, the median age was 40 years, and 87% had received HRT. Thirty-nine percent of cancer survivors had abnormal DEXA scan results compared to 15% of the control group, with the majority demonstrating osteopenia. The mean lumbar spine and femoral neck bone mineral densities (BMDs) were significantly lower in cancer patients. A history of gynecological cancer treatment was associated with significantly lower BMD in a multivariate logistic regression. CONCLUSIONS: Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.

Metabolic osteopathy in celiac disease: importance of a gluten-free diet.

Reduced bone mineral density (BMD) is frequently found in individuals with untreated celiac disease (CD), possibly due to calcium and vitamin D malabsorption, release of pro-inflammatory cytokines, and misbalanced bone remodeling. A gluten-free diet (GFD) promotes a rapid increase in BMD that leads to complete recovery of bone mineralization in children. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life. A GFD improves, but rarely normalizes, BMD in patients diagnosed with CD in adulthood. In some cases, nutritional supplementation may be necessary. More information on therapeutic alternatives is needed.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

[Fractures and chronic renal insufficiency]. / La patologia fratturativa nei diversi gradi di insufficienza renale cronica.

Chronic renal insufficiency (CRI) causes important modifications in the metabolism of phosphorus and calcium, to which frequently resulting in serious disorders of the skeleton, including demineralization, reduction of the bone resistance and a higher risk of fractures. Renal osteodystrophy is the term used to describe these disorders; they are generally heterogeneous and are classified according to the state of bone turnover into secondary hyperparathyroidism, adynamic bone, and osteomalacia. The incidence of hip fractures in the patients with CRI is higher than in the general population. Hip fractures are an important cause of morbidity and mortality. The evaluation of the fracture risk in the patients with different degrees of CRI is problematic, in particular because of the difficulty in identifying fractures, especially vertebral ones. The instrumental index that best expresses the fracture risk in the general population is bone mineral density (BMD); however, the relationship between low BMD and CRI is disputed. Bone disorders in patients with CRI have in fact a multifactorial pathogenesis and low BMD is not the only risk factor for fractures. Besides densitometric evaluation, also that vertebral morphometric evaluation would be desirable in patients with CRI. The fracture risk increases progressively with the severity of chronic renal disease and it is especially high in patients with renal insufficiency in more advanced-stages CRI (creatinine clearance<15-20 mL/min). However, not only in patients with severe CRI undergoing dialysis, but also in those with milder renal disease is the risk of bone fractures high.

Vitamin E provides protection for bone in mature hindlimb unloaded male rats.

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease.

BACKGROUND: Osteoporosis is a common complication of Crohn's disease. AIM: To study the effect on the bone mineral density of a bisphosphonate (pamidronate) given intravenously, in combination with oral calcium and vitamin D supplements, compared with oral calcium and vitamin D supplements alone. METHODS: Seventy-four patients with Crohn's disease and low bone mineral density at the lumbar spine and/or hip were randomized to receive either a daily dose of 500 mg of calcium with 400 IU of vitamin D alone or in combination with four three-monthly infusions of 30 mg of intravenous pamidronate over the course of 12 months. The main outcome measure was the change in bone mineral density at the lumbar spine and hip, measured by dual X-ray absorptiometry, at baseline and 12 months. RESULTS: Both groups gained bone mineral density at the lumbar spine and hip after 12 months. There were significant (P < 0.05) changes in the pamidronate group, with gains of + 2.6%[95% confidence interval (CI), 1.4-3.0] at the spine and + 1.6% (95% CI, 0.6-2.5) at the hip, compared with gains of + 1.6% (95% CI, - 0.1-3.2) and + 0.9% (95% CI, - 0.4-2.1) at the spine and hip, respectively, in the group taking vitamin D and calcium supplements alone. CONCLUSIONS: In patients with Crohn's disease and low bone mineral density, intravenous pamidronate significantly increases the bone mineral density at the lumbar spine and hip.

[Bone complication in diabetic subjects with good metabolic control and without any late complications: selected problems. Part I: calcium, phosphorus and magnesium metabolism]. / Powiklania kostne u chorych z dobrze wyrównana i niepowiklana cukrzyca typu 1 i 2--wybrane zagadnienia. Czesc I: Gospodarka wapniowo-fosforanowo-magnezowa.

The aim of the study was to evaluate whether in diabetics with good metabolic control and without any diabetic complications, disturbances of calcium, phosphorus and magnesium metabolism or hormonal regulation (parathormone/calcitonin) were present, and if they depended on type of diabetes, duration time of diabetes, kind of hypoglycaemic treatment, sex or age of patients. 83 subjects were examined, including: 14 with type 1 diabetes mellitus, 49 with type 2 diabetes mellitus and 20 healthy persons. All tests were performed in standarized low-calcium diet conditions. In basal conditions both serum concentrations and daily urine excretion of calcium, phosphorus, magnesium were estimated. Oral and intravenous calcium load tests with simultaneous parathormone, calcitonin, calcium, magnesium and phosphorus concentrations estimation were done. The final conclusions were as follow: Both in type 1 diabetes mellitus and type 2 diabetes mellitus subjects with good metabolic compensation and without advanced diabetic complications a tendency to early disturbances of calcium-phosphorus metabolism is observed. Physiological hormonal control (parathormone/calcitonin) is preserved. Correlations between mineral metabolism and type of diabetes, duration time of diabetes, daily insulin dose, body mass index and sex are observed. Kind of hypoglycaemic treatment has only slight influence on the mineral metabolism.

[Anemia and limping in a vegetarian adolescent]. / Anémie et boiterie chez un adolescent végétalien.

UNLABELLED: A vegan diet in the child and adolescent can induce severe bone sequelae by rickets and osteomalacia and megaloblastic anemia by cobalamin deficiency. CASE REPORT: A 15-year-old adolescent was hospitalized because of lameness and pallor. The lameness was explained by femoral epiphysiolysis caused by rickets with severe hypocalcemia. The pallor, jaundice and splenomegalia were due to cobalamin-deficiency megaloblastic anemia. A prolonged supplemental diet with calcium, vitamins D and B12 as well as orthopedic treatment stabilized the bone lesions. The megaloblastic anemia was cured by parenteral cobalamin. The adolescent and his brother were victims of a diet imposed by a cult and a lack of care due to their parents refusing that a vegan diet was the cause of the deficient pathology. Penal proceedings led to the incarceration of the parents and to the placement of the children. COMMENTS: Deficiencies in calcium and vitamins D and B12 may be severe in a child's development with a vegan diet. This case report reveals the social and legal problems of an inappropriate diet in infancy imposed by parents who are followers of a fundamentalist church. Beyond the management of children in cults, health professionals have to prevent, screen and supplement the deficient diet.

[Bone complications in diabetic subjects with good metabolic control and without any long-term complications--certain problems. Part III: The influence of hypertension and type 2 diabetes mellitus co-incidence of calcium, phosphorus and magnesium metabolism]. / Powiklania kostne u chorych z dobrze wyrównana i nie powiklana cukrzyca typu 1 i 2--wybrane zaganienia. Czesc III: Wplyw wspólistnienia nadcisnienia tetniczego z cukrzyca typu 2 na gospodarke wapniowo-fosforanowo-magnezowa.

Both high morbidity and potentiation of systemic complications emphasise significance of diabetes mellitus and hypertension co-incidence. The aim of the study was to analyse the influence of hypertension accompanied with type 2 diabetes mellitus on calcium phosphorus and magnesium metabolism. The study was performed in standard low-calcium diet conditions on the group of 49 patients with type 2 diabetes mellitus (among them 27 had hypertension), 14 patients with essential hypertension and 20 healthy persons. Both serum and urine concentration of creatinine, calcium, phosphorus, hydroxyproline, hydroxylysine and uric acid were analysed. Oral calcium load test was done. Serum alkaline phosphatase activity and oxalic acid urine excretion were also estimated. There were no significant differences between diabetic patients with and without hypertension as far as calcium, phosphorus or magnesium metabolism were concerned.

[The effect of smoking tobacco and drinking of alcohol and coffee on bone mineral density of healthy men 40 years of age]. / Wplyw palenia tytoniu, picia alkoholu i kawy na gestosc mineralna koscca obwodowego zdrowych mezczyzn po 40 roku zycia.

The aim of the study was to evaluate the effects of smoking, alcohol and coffee drinking on bone mineral content (BMC) in a group of 258 healthy men, aged 40-63, occupationally active inhabitants of Wroclaw. Trabecular, cortical and total BMC at the distal radius of the non-dominant hand were measured by pQCT method using the Stratec apparatus. The data concerning smoking, alcohol and coffee intake were obtained through a questionnaire. The significance of BMC differences between groups were tested using a one-way analysis of variance ANOVA. The extent of alcohol intake did not differentiate BMC values at the distal radius, whereas the significant detrimental effects of both smoking and coffee drinking on trabecular (but not cortical and total) BMC were revealed. Among healthy Polish males coffee drinking was associated with a significant reduction of trabecular BMC. Simultaneously, smokers and ex-smokers (when compared to never-smokers) had lower trabecular BMC.

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Administration of bisphosphonate prevents disuse bone atrophy induced by tail suspension.

We recently demonstrated that osteopenia induced by rat tail-suspension was associated with an initial increase in bone resorption. To study the significance of the increase in early bone resorption for osteopenia, we investigated whether administration of YH529, a third-generation bisphosphonate, prevents the development of osteopenia as evidenced by increased wet weight of the femur, together with its calcium and phosphorus contents, when compared with those of tail-suspended rats treated with the vehicle alone. These results suggested that the initial increase in bone resorption plays an important role in the development of osteopenia induced by tail suspension.

Bone and body mass changes during space flight.

Body mass, calcium and skeletal changes occur in humans who have worked in microgravity. Physiologic changes are seen as early as one week and are still occurring 312 days into space flight. The physiologic changes in bone and mineral metabolism may be among those which limits long duration space flight if an adequate countermeasure is not developed. The purpose of this paper is to summarize what is known about calcium dynamics and bone mineral changes as well as associated changes of body mass induced by space flight. The data reported is from a variety of studies conducted in both actual and simulated space flight.