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Back ground: Osteoporosis is a skeletal condition that affects the entire body. illness characterized by a decrease mass of bone, reduced Bone Mineral Density (BMD), deterioration of microarchitectural integrity and skeletal toughness, as a result of which bone fragility and fracture risk are raised, primarily at the spine and femur levels. Estradiol (E2)it is The most strong as well as widespread member of estrogen steroid hormone class. Estradiol obtained from their mother, their own gonads, and produced locally in their brains is administered to fetuses and infants. Calcium is most often associated with healthy bones and teeth, but it also plays an important part in blood clotting, muscle contraction, appropriate heart rhythms, and neuron activity. About 99 percent of the calcium in the body is stored in bones, with the remaining 1% found in blood, muscle, and other tissues. Intracellular calcium (Ca) levels are critical in the production of aldosterone. Potassium is a mineral that is required by all human tissues. It is commonly referred to as an electrolyte because it carries a little electrical charge that stimulates a variety of cell and nerve processes.. Total-body potassium (K+) concentration and proper distribution of K+ across the cell membrane are critical for good cellular function. Phosphorus is a mineral that is present in your bones. Phosphorus, like calcium, is necessary for the production of strong, healthy bones as well as the preservation of other aspects of your body's health.. Normal functioning kidneys can eliminate excess phosphorus from your blood. In marine settings, phosphorus (P) is one of the limiting macronutrients for algal development. Method: 100 patients clinically diagnosed as osteoporosis . tow study groups have been investigated: (25 in premenopause and 25 in postmenopause ). The Aim of study is determine the level of some parameters(albumin, calcium, potassium, phosphor, E2 ) in premenopausal osteoporosis and postmenopause osteoporosis and comparison to control group in women .Result : The current study was significant no difference in albumin level in osteoporosis, and decreased significant (P≤ 0.05) in levels of calcium and phosphor in osteoporosis,also increased significant(P≤ 0.05) in potassium level in osteoporosis,as well as there was a significance decreased (P≤ 0.05) in E2 hormone concentration of osteoporosis women compared to control .Conclusion : the albumin level no effected in osteoporosis when compared with control, the level of calcium and phosphor decreased in osteoporosis when compared with healthy women, the level of potassium increased in osteoporosis when compared with control group,the E2 hormone decreased in patients with osteoporosis, and this decreased is more significant in postmenopausal age than premenopause. [ABSTRACT FROM AUTHOR]

This study assessed differences in bone-mineral density (BMD) and lean and fat tissues between 5 age groups of White men age 65-93 years. Lean and fat tissues were measured with absorptiometry and anthropometry, and BMD, with dual-energy X-ray absorptiometry. Forearm, spinal, and femoral T scores were used to classify BMD as normal, osteopenic, or osteoporotic. A questionnaire evaluated previous physical activity, calcium intake, and bone fractures. Significantly lower values in body weight, lean tissue, and forearm BMD occurred in the older age groups. Significant, positive relationships were found between total lean tissue and radial, spinal, and hip BMDs. For the total group, osteopenic and osteoporotic T scores, respectively, were femoral neck 70.6% and 9.8%, radius 27.5% and 25.5%, and spine 25.5% and 7.8%. Differences in BMD values were found between levels of lifestyle factors (dietary calcium and history of previous fractures). In conclusion, elderly men should be encouraged to maintain adequate total lean tissue because of its association with BMD. [ABSTRACT FROM AUTHOR]

Alteration in the process of bone remodelling is associated with falls and fractures due to increased bone fragility and altered calcium functioning. The auditory system consists of skeletal structures and is, therefore, prone to getting affected by altered bone remodelling. In addition, the vestibule consists of huge volumes of calcium (CaCO3) in the form of otoconia crystals and alteration in functioning calcium levels could, therefore, result in vestibular symptoms. Thus, the present study aimed at compiling information from various studies on assessment of auditory or vestibular systems in individuals with reduced bone mineral density (BMD). A total of 1977 articles were searched using various databases and 19 full-length articles which reported auditory and vestibular outcomes in persons with low BMD were reviewed. An intricate relationship between altered BMD and audio-vestibular function was evident from the studies; nonetheless, how one aspect of hearing or balance affects the other is not clear. Significant effect of reduced bone mineral density could probably be due to the metabolic changes at the level of cochlea, secondary to alterations in BMD. One could also conclude that sympathetic remodelling is associated with vestibular problems in individual; however, whether vestibular problems lead to altered BMD cannot be ascertained with confidence. The studies reviewed in the article provide an evidence of possible involvement of hearing and vestibular system abnormalities in individuals with reduced bone mineral density. Hence, the assessment protocol for these individuals must include hearing and balance evaluation as mandatory for planning appropriate management. [ABSTRACT FROM AUTHOR]

Purpose Calcium nephrolithiasis is associated with an increased risk of osteoporosis and fracture. Hypercalciuria has been assumed to be pathogenic for bone loss in kidney stone formers, although this association was shown in small cross-sectional studies. We explored the association of urine calcium with bone mineral density in kidney stone formers. Materials and Methods We retrospectively studied bone mineral density in kidney stone formers. Excluded were subjects with hypercalcemia, chronic bowel disease, primary hyperparathyroidism, distal renal tubular acidosis or endogenous creatinine clearance less than 40 ml per minute. We included 250 males and 182 females subdivided into 145 who were estrogen treated and postmenopausal, and 37 who were nonestrogen treated and postmenopausal. We assessed the association of lumbar spine and femoral neck bone mineral density with 24-hour urine calcium on random and restricted diets, and while fasting using univariable and multivariable models adjusting for body mass index, urine sodium and sulfate. Results On multivariable analysis no significant association was found between urine calcium on a random or a restricted diet, or during fasting conditions and femoral neck or lumbar spine bone mineral density in men and estrogen treated women. In estrogen untreated women lumbar spine bone mineral density inversely correlated with urine calcium on the restricted diet (r = −0.38, p = 0.04 and adjusted r = −0.45, p = 0.02) and in the fasting state (r = −0.42, p = 0.05). Conclusions Unlike in previous small cross-sectional studies we found no significant relationship between urine calcium and bone mineral density in a large group of calcium kidney stone formers. However, a significant inverse relationship was found in estrogen untreated kidney stone formers only. This study suggests that mechanism(s) other than hypercalciuria explain the lower bone mineral density and the higher fracture risk in patients who are kidney stone formers. It also highlights the role of estrogen on bone integrity. [ABSTRACT FROM AUTHOR]

Osteoporosis means bones ("osteo") that are porous ("porosis"), or weak. When your body loses calcium, your bones become weaker and more likely to break. [ABSTRACT FROM AUTHOR]

The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2-4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, β-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were independent risk factors for osteoporosis. Genetic polymorphisms of GALNT3 and VDR were closely associated with osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) of patients with hemoglobin H (HbH) disease.Methods: BMD and BMC were measured by dual energy X-ray absorptiometry of the lumbar spines and femur neck in 21 patients with Hb H disease over the age of 10 years. An association of BMD with sex, age, hemoglobin, calcium, phosphorus, and serum ferritin level was also evaluated.Results: Prevalence of BMD below the expected range for age in the lumbar spine and femur neck region in patients with HbH disease were 33.3 and 14.3 %, respectively. Lumbar BMD was significantly lower in the patients compared to healthy individuals (median (min-max) 0.725 (0.595-0.924) vs. 1.061 (0.645-1.238), P < 0.001)). There was no significant relationship between BMD in the lumbar and femur neck with any of the evaluated variables (P value >0.05).Conclusion: Data regarding bone density in HbH disease is limited; osteoporosis as a common complication of β-thalassemia intermedia syndrome should be considered even in HbH which shows its prevalence is less than β-thalassemia intermedia. [ABSTRACT FROM AUTHOR]

Introduction: The mechanical competence parameter (MCP) of the trabecular bone is a parameter that merges the volume fraction, connectivity, tortuosity and Young modulus of elasticity, to provide a single measure of the trabecular bone structural quality. Methods: As the MCP is estimated for 3D images and the Young modulus simulations are quite consuming, in this paper, an alternative approach to estimate the MCP based on artificial neural network (ANN) is discussed considering as the training set a group of 23 in vitro vertebrae and 12 distal radius samples obtained by microcomputed tomography (μCT), and 83 in vivo distal radius magnetic resonance image samples (MRI). Results: It is shown that the ANN was able to predict with very high accuracy the MCP for 29 new samples, being 6 vertebrae and 3 distal radius bones by μCT and 20 distal radius bone by MRI. Conclusion: There is a strong correlation (R2 = 0.97) between both techniques and, despite the small number of testing samples, the Bland-Altman analysis shows that ANN is within the limits of agreement to estimate the MCP. [ABSTRACT FROM AUTHOR]

Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 µg/kg once daily (TPD × 1 group), 40 µg/kg three times daily (TPD × 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (µCT) and histological analysis were performed. Longitudinal µCT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD × 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH. [ABSTRACT FROM AUTHOR]

Introduction: Calcium is the most abundant mineral in our body with varied functions and its dietary deficiency leads to osteoporosis, besides playing a significant role in the pathogenesis of other diseases. The data regarding dietary calcium intake (DCI) among postmenopausal women in urban areas of South India is limited. Objectives: This study was aimed to assess DCI and physical activity among postmenopausal women. The risk factors for a low intake of dietary calcium were also assessed. Materials and Methods: A cross-sectional study was done among 106 postmenopausal women selected by systematic random sampling from the city of Erode, Tamil Nadu, India. DCI and physical activity were measured using validated questionnaires. Results: The mean DCI was 632.72 ± 28.23 mg/day. The proportion of women consuming less than 800 mg/day of dietary calcium was 74.5%. Only 10.4% of the women studied (11 out of 106) were on calcium supplements while 55% had low physical activity. A low knowledge score [adjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 1.31-20.42] and a low socioeconomic status (SES) score of the family (adjusted OR: 4.00; 95% CI: 1.32-12.11) were significantly associated with low DCI after adjusting the age, dietary preferences, and educational and occupational statuses. Conclusions: DCI was below the Recommended Dietary Allowance (RDA) and the majority of postmenopausal women were physically inactive, indicating the need for better education regarding DCI and the need for calcium supplements and physical activity, all of which can contribute to the prevention of the consequences of osteoporosis. [ABSTRACT FROM AUTHOR]

Eldecalcitol (ELD), a new active vitamin D analog developed in Japan, has attracted attention as an effective osteoporotic therapeutic drug. However, because ELD leads to greater calcium absorption than does conventional active vitamin D, it has yet to be used in patients with renal insufficiency. Therefore, we evaluated the efficacy and safety of ELD treatment in 27 postmenopausal women receiving maintenance dialysis in our institution and underwent ELD treatment (starting at 0.5 μg/day) for 6 months. The mean serum albumin-corrected calcium (Ca) level was significantly increased following treatment (9.01 ± 0.60 before versus 9.56 ± 0.55 after treatment, mean ± SD). Severe hypercalcemia was prevented through cessation or adjustment of the dosage of calcium-containing phosphate binders or existing active vitamin D. The mean serum phosphorus and intact parathyroid hormone levels were well-controlled throughout. The median levels of bone turnover markers, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b were significantly decreased. The mean lumbar spine bone mineral density (BMD) was increased, a significant difference being observed in age-matched Z-scores (−0.60 ± 1.6 versus −0.36 ± 1.5, p = 0.018). The average change in lumbar spine BMD after ELD treatment was 3.10 %, and in patients with a T-score of <−4.0, it was 5.63 %. There was no effect on forearm BMD. Although this study is based on short-term observation in a single institution, our results suggest that ELD could be used to increase bone density in dialysis patients. [ABSTRACT FROM AUTHOR]

Copper, magnesium, zinc and calcium status were measured in postmenopausal women with osteoporosis (n = 23) and osteopenia (n = 28) as classified on the basis of the T-score of the femur neck and dual energy X-ray absorptiometry results. Anthropometric indices, dietary intake and serum copper, magnesium, zinc and calcium were assessed. The results of our study showed that the mean dietary intake of magnesium, zinc and calcium in post-menopausal women with low bone density were significantly lower than recommended dietary allowance. The mean serum levels of zinc (P = 0.001) and copper (P = 0.000) were significantly lower than normal range and 40.4% of this participants had serum magnesium levels lower than normal range. No statistically significant differences were observed between the osteopenic and osteoporotic groups with respect to serum levels and dietary intakes of copper, calcium, magnesium and zinc. Due to the mineral deficiency in post-menopausal women with low bone density and the key role of minerals on bone health, supplementation with magnesium, I calcium, zinc and perhaps copper recommended. [ABSTRACT FROM AUTHOR]

Background Osteoporosis has become a major public health issue. Among various factors affected bone health, not only dietary calcium and phosphorus intakes, but also the dietary calcium/phosphorus ratio could relate to bone health. Therefore, we evaluated whether dietary calcium and phosphorus intakes, and dietary calcium/phosphorus ratio are associated with bone mass in Korean adults ≤ 20 years of age. Methods The analysis used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional survey of Korean civilians, conducted from January to December 2010. A total of 4,935 participants (2,309 men and 2,626 women) were analyzed in this study. Dietary calcium and phosphorus intakes of the participants were estimated using 24-h dietary recall. Bone mass densities for the whole body, femoral neck, and lumbar spine were measured by dual-energy X-ray absorptiometry. Results Dietary calcium intake and dietary calcium/phosphorus ratio were positively related to bone mass density for femoral neck in men ≤ 50 years of age (p = 0.046 and 0.041, respectively). Dietary calcium intake showed positive associations with bone mass density for whole body in premenopausal women (p = 0.022). Conclusions Increased calcium intake and high dietary calcium/phosphorus ratio might have favorable effects on bone mass in Korean adults. Additional gender- and age-specific studies are needed to further identify the influence of calcium and phosphorus intakes, and the dietary calcium/phosphorus ratio on bone mass. [ABSTRACT FROM AUTHOR]

Both transcellular, vitamin-D dependent and the quantitatively more important paracellular, nonsaturable calcium absorption depend on the presence of free calcium ions or on the presence of reactive precursors for free calcium ions in the intestines. Complex binding of calcium preventing precipitation of calcium salts under the neutral to slightly alkaline conditions of the intestines accordingly determines calcium absorbability. The presence of suitable ligands for calcium complexation is important already when the partly digested food is transferred from the acidic stomach to the neutral intestines. The competitive complex binding and precipitation of calcium decisive for subsequent absorption in the intestines and further for bioavailability is accordingly influenced by the calcium speciation in the stomach resulting from food digestion. Calcium salt solubilities relative to calcium binding strength in complexes are the thermodynamic factors controlling the level of free calcium ions matching the free calcium level allowing facile absorption. However, kinetic factors like rates of precipitation and rates of complex formation and of complex dissociation seem of equal importance, especially when the same anion precipitates calcium and forms complexes with calcium as for hydroxycarboxylates like lactate. Spontaneous supersaturation resulting from isothermal dissolution overshooting during digestion or from gradually increasing pH is suggested to increase calcium mobility and bioavailability and needs to be incorporated in current theories for calcium bioavailability. Understanding the dynamic aspects of calcium speciation throughout digestion, and not only in the intestines, will also allow for better calcium fortification strategies to ensure optimized calcium bioavailability. [ABSTRACT FROM AUTHOR]

After adulthood, changes in the skeleton are slow and takes years for accruing or losing any appreciable amount of bone mass. Proper interpretation of studies that evaluate the effect of nutrients (like calcium, vitamin D) and anti-resorptive agents (like bisphosphonates) on bone mass is important so that the true effect of the agent is measured correctly. In this report, we are highlighting two issues of utmost importance for correctly interpreting interventional studies for osteoporosis. One issue is the bone remodelling transient (BRT). It refers to a transient change in bone mineral density (BMD) by any agent that reduces remodeling space temporarily. This change is, however, not sustained for a long period and can be misinterpreted as a true gain in bone mass. The second issue is difference between calcium balance and bone balance. Calcium balance is the difference between the amount of calcium ingested in a day and the amount of calcium lost in that day. Recommendations for dietary calcium intake are based on calcium balance studies that presume calcium balance as an equivalent for bone balance. However, these are two different entities and need to be distinguished. Dietary calcium requirements should be established by bone balance studies using bone densitometry, not by calcium balance studies. [ABSTRACT FROM AUTHOR]

Objective(s): Pantoprazole, is a proton pump inhibitor (PPI) prescribed for the treatment of upper gastrointestinal disorders, which in high doses has been suggested to decrease calcium absorption leading to hypocalcaemia and therefore osteoporosis. The aim of this study was to assess whether pantoprazol, could alter the rate of orthodontic tooth movement (OTM) in rats. Materials and Methods: A time course study was established using 72 rats which were divided into six groups of 12 samples each (four: vehicle; eight: pantoprazole + vehicle). Pantoprazole at a dose of 200 mg/kg suspended in carboxymethyl cellulose (0.25 percent) was administered by a gastric tube. The upper incisors and first molars were ligated by a 5 mm nickel-titanium closed-coil spring to deliver an initial force of 60 g. Animals were euthanized two weeks after orthodontic treatment followed by assessment of tooth movement and histomorphometric evaluation of the detached maxillae. Lateral skull radiographs were obtained once a week, starting from the first day to the 6th week of the study. OTM and bone density data were analyzed using independent sample t-test and repeated measures ANOVA. Results: No significant changes in OTM measurements and optical density were observed in vehicle-receiving animals during the study (P=0.994). OTM was significantly increased after six weeks pantoprazole therapy which continued until the 7th week of the experiment (P=0.007). Optical density significantly increased in the pantoprazole-treated rats after six weeks. Conclusion: Long term PPI therapy at high doses could lead to osteoporosis and enhanced OTM. [ABSTRACT FROM AUTHOR]

Introduction. Calcium and vitamin D are essential structural components of the skeletal system, which prevent osteoporosis after menopause. However, there is a controversial debate on the association between the intake of calcium and vitamin D supplements and the increased risk of formation of kidney calculi in postmenopausal women. which yet have to be confirmed. This study aimed to compare the metabolic changes after supplementation of calcium and vitamin D and examine the risk of stone formation. Materials and Methods. Fifty-three postmenopausal women referred to rheumatology clinic who had no history of kidney calculi, bone diseases (apart from osteoporosis), metabolic, and rheumatic disorders and had not been receiving calcium, diuretics and calcitonin were investigated. Renal ultrasonography and blood tests were performed and the urine calcium levels were measured for a period of 24 hours for all patients. The examinations were repeated after a 1- year period of treatment with supplemental calcium (100 mg/d) and vitamin D (400 IU/d) and compared with the data before the treatment. Results. After 1 year, asymptomatic lithiasis was confirmed in 1 of 53 patients (1.9%) using ultrasonographic examination. No significant differences were found between the 24-hour urine and blood calcium levels before and after the treatment. Conclusions. Our findings showed that oral intake of calcium and vitamin D after 1 year has no effect on the urinary calcium excretion rate and the formation of kidney calculi in postmenopausal women. [ABSTRACT FROM AUTHOR]

Aim Measurements of salivary calcium level may be a useful screening tool for osteoporosis in postmenopausal women. The purpose of this study was to clarify whether this measure is valid compared with dual-energy X-ray (Bone Mineral Density) screening tools in osteoporosis. Methods A case-control study was carried out in 40 postmenopausal women with osteoporosis ( T-score ≤ −2.5) and 40 women without osteoporosis ( T-score > −1 bone mineral density). Salivary samples were collected and calcium concentrations were measured and expressed as mg/d L. Receiver operating characteristic curve analyses was used to determine the optimal cut-off thresholds for salivary calcium in healthy postmenopausal women. Results The cut-off point for salivary calcium was 6.1 mg/d L. The sensitivity and specificity, respectively, for identifying women with osteoporosis, were 67.5 (95% CI 52.33-82.67) and 60% (95% CI 44.62-75.38). The area under curve ( AUC) was 0.678 (95% CI 0.56-0.79), the positive predictive value ( PPV) was 62.79 (95% CI 47.74-77.84) and negative predictive value ( NPV) was 64.86% (95% CI 49.27-80.46). The positive likelihood ratio was 1.688 and the negative likelihood ratio was 0.542. Conclusions Salivary calcium concentration discriminates between women with and without osteoporosis and constitutes a useful tool for screening for osteoporosis. [ABSTRACT FROM AUTHOR]

Aim This Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with osteoporosis ( OP), using the best available evidence. Methods A literature search using Pub Med ( MEDLINE) and The Cochrane Library identified all relevant articles on OP and its assessment, diagnosis and treatment, from 2005, to update from the previous edition published in 2006. The studies were assessed and the level of evidence assigned; for each statement, studies with the highest level of evidence were used to frame the recommendation. Results This article summarizes the diagnostic and treatment pathways for OP, highlighting the new data that have changed the way we assess and treat OP. Instead of starting treatment based on bone mineral density alone, there has been a move to assessing 10-year fracture risk before treatment, using tools such as the Fracture Risk Assessment Tool ( FRAX). There has been a re-evaluation on calcium supplementation and more emphasis on the importance of vitamin D. There has been concern about the potential adverse effects of the long-term usage of bisphosphonates, which we have discussed fully. New drugs that have been licensed since 2006 in Malaysia have been included. Conclusions Adequate intake of calcium (1000 mg from both diet and supplements) and vitamin D (800 IU) daily remain important in the treatment of OP. However, in confirmed OP, pharmacological therapy with anti-resorptives is the mainstay of treatment. Patients need to be regularly assessed while on medication and treatment adjusted as required. [ABSTRACT FROM AUTHOR]

Abstract: Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, and it is a serious threat to human lives. We previously showed that the N-terminal peptide analog of human parathyroid hormone (Pro-Pro-PTH(1–34)) enhanced plasma calcium concentration. In this paper, we study the impact of PTH N-terminal fragment analog on the structure, component, and mechanical properties of the rat bones. Daily subcutaneous injections of Pro-Pro-hPTH (1–34) induces 26.5–32.8% increase in femur bone mineral density (BMD), 23.0–34.2% decrease the marrow cavity or increase in trabecular bone area. The peptide also increases 16.0–59.5%, 28.8–48.2% and 14.0–17.8% of bone components of calcium, phosphorus and collagen, respectively. In terms of mechanic properties, administration of the peptide elevates the bone rigidity by 45.4–76.6%, decreases the flexibility by 23.0–31.6%, and improves modulus of elasticity by 32.8–63.4%. The results suggest that Pro-Pro-hPTH (1–34) has a positive effect on bone growth and strength, and possesses anti-fracture capability, thus a potential candidate for the application for the treatment of osteoporosis. [Copyright &y& Elsevier]

Abstract: Purpose: Metabolic bone disorders are very common in the elderly population. As fingernail clippings are easily available for analysis, this makes them an interesting screening instrument for stored mineral components in the body. Measurements of calcium concentrations in fingernail clippings are thought to give some insight into their value as an alternative screening test for metabolic bone disorders and our aim was to determine whether fingernail calcium concentrations could be used for this purpose. Patients and methods: This is a cross-sectional study, carried out in a Geriatric medicine outpatient clinic of a university hospital. A total of 159 patients with a mean age of 72.1±5.8 years were involved. Fingernail calcium levels were analyzed with atomic absorption spectrophotometry. Results: There was no statistically significant difference in nail calcium levels between osteoporotic and non-osteoporotic patients and similarly between vitamin D deficient and normal patients. The correlation between nail calcium concentrations and femur neck t-score and serum 25-OH vitamin D levels was very weak and non-significant. Conclusion: We found no change in nail calcium concentrations in osteoporosis and vitamin D deficiency, and therefore nail calcium measurements do not seem to be a good alternative screening instrument for metabolic bone disorders in the elderly. [Copyright &y& Elsevier]

Purpose: Fragility fractures are characterized by a low energy trauma and should be considered as potentially osteoporosis-related fractures. This study aimed to determine whether the orthopedic surgeons' awareness could increase the osteoporosis management rate in patients with fragility fractures. Method: This study was undertaken in three phases: evaluation of existing practice patterns, educational intervention and evaluation of the effect of the training. During the study period, orthopedic surgeons who worked at academic hospitals attended five educational sessions and were provided with posters and brochures. Patients were interviewed at sixth and twelfth months after discharge using an evaluation questionnaire regarding their perceptions of the barriers to osteoporosis treatment. Results: Seventy-two orthopedic surgeons volunteered to participate in the study between June 2008 and December 2011. The patients were followed for a minimum of 1 year. Rate of calcium and vitamin D prescriptions increased from 10 to 91 %. The rate of bisphosphonate administration reached to 73 %. The number of follow-up evaluations did not differ significantly. Conclusion: The detection and medication rates for osteoporosis in patients with fragility fractures increased more than tenfold after the intervention program. [ABSTRACT FROM AUTHOR]

Key content Osteoporotic fractures are associated with increased morbidity and mortality., Clinical history and bone densitometry can identify individuals at risk for osteoporotic fractures., Treatment is available to prevent and treat osteoporosis., Learning objectives Identify populations at risk for osteoporotic fractures., Make the diagnosis of osteoporosis., Decide appropriate treatment for the prevention or treatment of osteoporosis., Ethical issues Maximising health benefit while minimising financial implications. [ABSTRACT FROM AUTHOR]

Abstract: The endocrine action of plasma 1,25-dihydroxyvitamin D plays a key role in the regulation of plasma calcium and phosphate homeostasis with activities on the intestine, kidney and bone. A current, controversial question is whether vitamin D exerts direct actions on bone cells to regulate bone mineral homeostasis. Results from clinical, rodent model and in vitro studies on human bone cells provide an impressive body of data to support this proposal particularly at the level of serum 25-hydroxyvitamin D status. Each of the major bone cell types is capable of metabolising vitamin D to the active metabolite, 1,25-dihydroxyvitamin D. Thus under conditions when bone tissue synthesis of 1,25-dihydroxyvitamin D is optimal, vitamin D activity enhances bone mineral status. Dietary calcium and phosphate intakes are the critical environmental cues together with vitamin D status to determine whether 1,25-dihydroxyvitamin D exerts an anabolic or catabolic action on bone mineral status. [Copyright &y& Elsevier]

In series of three experiments young women's attention patterns were analyzed using eye tracking to deteremine the most effective viewing format and message content for presenting osteoporosis prevention ads. In Experiment 1A ads including both images and text attracted more attention than the image-only or text-only formats, p < .01. Experiment 1B revealed that osteoporosis ads attract significantly less attention than fashion and beauty ads ( p < .01) and exercise apparel ads ( p < .01). The last experiment revealed that osteoporosis ads featuring exercise messages were more effective at capturing attention than those promoting increased calcium and vitamin D consumption ( p < .01). These findings may inform the way in which future osteoporosis prevention ads are created. [ABSTRACT FROM AUTHOR]

The conformationally flexible secosteroid, 1α,25(OH)2vitamin D3 (1α,25(OH)2D3) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH)2D3, the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH)2D3. By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH)2D3/VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection. [ABSTRACT FROM AUTHOR]

Abstract: Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac5c1, Aib3, Leu8, Gln10, Har11, Ala12, Trp14, Asp17]PTH(1-17)-NH2), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K13-D17 side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40–320nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40–160nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats. To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range. [Copyright &y& Elsevier]

Abstract: The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound’s chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. [Copyright &y& Elsevier]

Abstract: Osteoporosis, which has become a serious public health concern, is influenced by diet, especially calcium intake. Dairy products are a good source of calcium, but plant calcium may also be important in populations that do not consume a large amount of milk. The purpose of the present study was to examine the hypothesis that calcium from vegetable sources is associated with osteoporosis risk and bone mineral density in postmenopausal Korean women with osteoporosis and age-matched controls (N = 144). The results of multivariate-adjusted regression analyses indicated that the intake of calcium, plant calcium, potassium, vitamin A, carotene, vitamin B1, niacin, vitamin E, vitamin C, and vegetables was associated with significantly reduced risk of osteoporosis after adjusting for age, body mass index, hormone replacement therapy, and energy intake. In addition, intake of vegetables alone, as well as calcium, plant calcium, potassium, and antioxidant vitamins (vitamin C, vitamin E, β-carotene), which are abundant in vegetables, was significantly and positively associated with bone mineral density. However, in this population of low-dairy consumers, intake of calcium from meat and dairy products was not related to risk of osteoporosis and bone mineral density. Our results suggest that high dietary intake of calcium, especially plant calcium, reduces the risk of osteoporosis and increased bone mineral density in postmenopausal Korean women. Vegetables may be an important source of calcium and may also provide vitamins and minerals that exert additional beneficial effects on the bone. [Copyright &y& Elsevier]

Abstract: Introduction: Osteoporosis and its consequent fractures is a major public health problem. Aim: To formulate a position statement on the use of bone densitometry in screening postmenopausal women for osteoporosis and in their management. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Bone densitometry has an important role in screening postmenopausal women for osteoporosis. For higher sensitivity and specificity, there may be a stronger case for screening in later life, depending on the extent to which risk factors add to the value of bone mineral density tests. [ABSTRACT FROM AUTHOR]

Abstract: We investigated whether those who experience the greatest increases in bone turnover in response to parathyroid hormone (PTH) therapy are the same as those who experience elevations in calcium levels. Baseline and follow-up procollagen type I N propeptide (PINP), bone-specific alkaline phosphatase (BAP), C-terminal telopeptide (CTX), and serum and urinary calcium levels were analyzed post hoc from the 119 postmenopausal women with osteoporosis randomized to PTH(1–84) in the Parathyroid Hormone and Alendronate trial. Short-term changes in the markers of bone turnover were highly correlated with one another (r =0.57–0.87, p <0.001). In contrast, change in serum calcium correlated only modestly with changes in markers of formation (r =0.22–0.30, p ≤0.02) and did not correlate significantly with change in CTX (r =0.13, p =0.18). Participants who experienced hypercalcemia experienced greater 3-mo changes in BAP than those who did not (78% vs. 42% increase in BAP, p =0.04), with similar trends for PINP and CTX. In conclusion, the use of 1 marker of bone turnover, rather than multiple markers, may be sufficient to assess biochemical response to PTH(1–84). The relationship between bone turnover marker and calcium responses to PTH(1–84) is modest and does not suggest a profound, broadly heightened responsiveness of certain individuals to therapy. [Copyright &y& Elsevier]

Bone geometry and tissue material properties jointly govern whole-bone structural behavior. While the role of geometry in structural behavior is well characterized, the contribution of the tissue material properties is less clear, partially due to the multiple tissue constituents and hierarchical levels at which these properties can be characterized. Our objective was to elucidate the contribution of the mineral phase to bone mechanical properties across multiple length scales, from the tissue material level to the structural level. Vitamin D and calcium deficiency in 6-week-old male rats was employed as a model of reduced mineral content with minimal collagen changes. The structural properties of the humeri were measured in three-point bending and related to the mineral content and geometry from microcomputed tomography. Whole-cortex and local bone tissue properties were examined with infrared (IR) spectroscopy, Raman spectroscopy, and nanoindentation to understand the role of altered mineral content on the constituent material behavior. Structural stiffness (-47%) and strength (-50%) were reduced in vitamin D-deficient (-D) humeri relative to controls. Moment of inertia (-38%), tissue mineral density (TMD, -9%), periosteal mineralization (-28%), and IR mineral:matrix ratio (-19%) were reduced in -D cortices. Thus, both decreased tissue mineral content and changes in cortical geometry contributed to impaired skeletal load-bearing function. In fact, 97% of the variability in humeral strength was explained by moment of inertia, TMD, and IR mineral:matrix ratio. The strong relationships between structural properties and cortical material composition demonstrate a critical role of the microscale material behavior in skeletal load-bearing performance. [ABSTRACT FROM AUTHOR]

Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests. Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests. During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens. We found moderate correlation between paired SUCCR and 24HUC specimens ( r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland–Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)2D. The model improved diagnostic sensitivity to 100% and decreased Bland–Altman bias of the SUCCR to +0.06 mg/kg/24-hour. We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR’s accuracy. Future studies must verify this correction before clinical implementation. [ABSTRACT FROM AUTHOR]

Abstract: The purposes of this study were to determine the role of bone mineral density (BMD) and mood in influencing health-related behaviors of serious leisure male athletes (cyclists and triathletes) at risk for osteoporosis. A cross-sectional design evaluated BMD in 18–60-yr-old serious leisure male cyclists by dual-energy X-ray adsorptiometry (DXA). Activity was measured using the International Physical Activity Questionnaire; personality was assessed using the NEO-60; and quality of life using Short-Form Health 12 (SF-12). Participants completed an online survey questionnaire after completing their DXA testing a minimum of 3mo before assessing health-related behaviors and general attitudes toward general health and well-being. Forty-two (61.9%) participants responded to the follow-up questionnaire. Serious leisure male athletes are more likely to initiate significant health-related behavioral changes after learning of their bone density results including calcium supplementation and weight-bearing exercise. Men with low BMD (LBMD) had higher openness subscales on NEO-60 compared with men with normal BMD. SF-12 mental and physical health scores were significantly lower in men with LBMD. Perhaps, the interaction and interplay of genetics, activity and behaviors, and aspects of mental and psychological functions contribute to their reduction in BMD and heightened risk for fracture. Findings from this study suggest that early BMD testing in “serious athletes” has important clinical relevance for their potential risk for osteoporosis in the future. [Copyright &y& Elsevier]

Purpose: This study was done to determine the level of awareness and self-efficacy and their relationships to osteoporosis among young women. Methods: The participants were 309 young women living in Seoul. The data were collected using questionnaires from July to September 2009. The Osteoporosis Awareness Scale consists of five areas with a total of 31 questions and the Self-efficacy Scale consists of 18 questions. Data were analyzed using descriptive analysis, t-test, ANOVA, Scheffétest and Pearson's correlation coefficients. Results: The average level for osteoporosis awareness was 2.22, of a possible 4.00 and significant difference were related to participants' previous encounter with any information about osteoporosis, behavior to prevent osteoporosis, experience of weight control, and frequency of vegetable and calcium-rich foods intake. The average level of self-efficacy for osteoporosis was 2.81, of a possible 4.00 and significant difference related to participants' educational level, occupation, behavior to prevent osteoporosis, smoking, method of weight control, regular exercise, and frequency of vegetable and calcium-rich foods intake. There were significant positive correlations among awareness and self-efficacy about osteoporosis. Conclusion: This study suggests that health care professionals need to provide effective interventions for young women to enhance their osteoporosis awareness and self-efficacy for preventing osteoporosis. [ABSTRACT FROM AUTHOR]

The article focuses on the approaches used to manage postmenopausal osteoporosis and promote bone health among postmenopausal women. It states that postmenopausal women have high risk of having bone fractures and osteoporosis. Among the strategies used to manage postmenopausal osteoporosis include adequate intake of vitamin D and calcium and having a bone-healthy lifestyle, which consist of smoking cessation and restriction of alcohol and caffeine intake.

Abstract: We explored the possibility of using natural calcium (Ca) isotope variations in the urine (δ44/40Caurine) as a proxy for the Ca balance in the human body. We chose two test persons extremely different in their health status, gender and age (4-year-old healthy boy and a 60-year-old woman known to suffer from osteoporosis). During a 5 day interval the Ca isotope composition of the individual diet (δ44/40Cadiet) was monitored for both test persons to be in general agreement to the Ca isotope composition of the normal western European diet (∼−1.02±0.1‰). However, measurements showed that (1) δ44/40Caurine of both test persons are ∼1.37 and ∼2.49‰, respectively, heavier than δ44/40Cadiet and that (2) the δ44/40Caurine-boy is ∼1.1‰ heavier when compared to the value of the woman. The individual offset between diet and test persons is interpreted to reflect individual Ca reabsorption rates in the kidneys being the result of Rayleigh type Ca isotope fractionation related to the partitioning of Ca between the glomerular filtrate and filtered residue. The relative difference between δ44/40Caurine-boy and δ44/40Caurine-woman of ∼1.1‰ may reflect individual differences in the balance of bone mineralization and demineralization processes related to age, gender and health status. By arbitrarily defining an equilibrium value for Δ44/40Cadiet-urine of −1.93‰ being the arithmetic mean of δ44/40Caurine for both test persons the measured δ44/40Caurine values may be applied to model the individual bone mineralization and demineralization processes in a qualitative way. Note, second order influences of intestinal Ca absorption during sequestration of Ca between intestine and blood have to be subject of further studies. [Copyright &y& Elsevier]

Abstract: Recent progress has been made in our understanding of the functional role of the seven-transmembrane-spanning extracellular calcium-sensing receptor (CaSR) in bone cells. Both in vitro and in vivo data indicate that the CaSR is a physiological regulator of bone cell metabolism. The CaSR regulates the recruitment, differentiation and survival of osteoblasts and osteoclasts through activation of multiple CaSR-mediated intracellular signaling pathways in bone cells. This raises the possibility that the bone CaSR could potentially be targeted by allosteric modulators, either agonists (calcimimetics) or antagonists (calcilytics) to control bone remodeling. The therapeutic potential of CaSR agonists or antagonists in bone cells is however hampered by their effects on the CaSR in nonskeletal tissues. Rather, direct targeting of the bone CaSR may be of potential interest for the treatment of bone diseases. Targeting the bone CaSR using a bone-seeking CaSR agonist offers a potential mean to modulate bone cell metabolism. The development of drugs that preferentially target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis. [Copyright &y& Elsevier]

Abstract: The differentiation and degree of the effects of mineral content and/or morphology on bone quality remain, to a large extent, unanswered due to several microarchitectural particularities in spatial measuring fields (e.g., force transfer, trajectories, microcalli). Therefore, as the smallest basic component of cancellous bone, we focused on single trabeculae to investigate the effects of mineralization and structure, both independently and in superposition. Transiliac Bordier bone cores and T12 vertebrae were obtained from 20 females at autopsy for specimen preparation, enabling radiographical analyses, histomorphometry, Bone Mineral Density Distribution (BMDD) analyses, and trabecular singularization to be performed. Evaluated contact X-rays and histomorphometric limits from cases with osteoporotic vertebral fractures generated two subdivisions, osteoporotic (n =12, Ø 78 years) and non-osteoporotic (n =8, Ø 49 years) cases, based on fracture appearance and bone volume (BV/TV). Measurements of trabecular number (Tb.N.), trabecular separation (Tb.Sp.), trabecular thickness (Tb.Th.), trabecular bone pattern factor (TBPf) and eroded surface (ES/BS) were carried out to provide detailed structural properties of the investigated groups. The mechanical properties of 400 rod-like single vertebral trabeculae, assessed by three-point bending, were matched with mineral properties as quantified by BMDD analyses of cross-sectioned rod-like and plate-like trabeculae, both in superposition and independently. Non-osteoporotic iliac crests and vertebrae displayed linear dependency on structure parameters, whereas osteoporotic compartments proved to be non-correlated with bone structure. Independent of trabecular thickness, osteoporotic rod-like trabeculae showed decreases in Young''s modulus, fracture load, yield strength, ultimate stress, work to failure and bending stiffness, along with significantly increased mean calcium content and calcium width. Non-osteoporotic trabeculae showed biomechanically beneficial properties due to a homogeneous mineralization configuration, whereas osteoporotic trabeculae predominantly demonstrated various mineralized bone packets, eroded surfaces, highly mineralized cement lines and microcracks. The Young''s moduli of single trabeculae exhibited significantly negative linear correlations with trabecular thickness. Because of increased, but inhomogeneously distributed, calcium content, osteoporotic trabeculae may be subject to shear stresses that render bone fragile beyond structure impairment due to cracks and lacunae. [Copyright &y& Elsevier]

Background: Chronic antiepileptic therapy has been associated with metabolic bone diseases including osteomalacia and osteoporosis. The object of this study was to assess the effect of first line anticonvulsants on bone density and vitamin D levels in Iranian ambulatory patients. Methods: We conducted a cross-sectional study assessing bone density with dual energy Xray absorptiometry at the hip and lumbar spine in 90 outpatients receiving anticonvulsants and 90 normal subjects matched for age, sex, and body mass index. Plasma total calcium, intact parathyroid hormone, total alkaline phosphatase in addition to 25 hydroxy vitamin D were also determined in both groups. Results: The mean (±SD) bone density in patients treated with antiepileptic drugs was lower at the spine (T Score= -084±1.18 vs. -0.5±1.18, P< 0.05) and femoral neck (T Score= -0.83±1.11 vs. -0.46±1.1, P<0.05), compared to the control group of subjects. In addition, serum total alkaline phosphatase was significantly higher in patients (246.5±127 vs. 190±65.3, P=0.004), but the total calcium, parathyroid hormone and 25 hydroxy vitamin D did not differ significantly between patients and controls. Conclusion: Our results suggest that maintenance therapy with antiepileptic drugs may decrease bone mass. These data also suggest a higher bone turnover rate in those receiving anticonvulsants. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effect of marked weight loss after long limb-biliopancreatic diversion (BPD-LL) on bone mass and serum calcium, 25-OH-vitamin D and parathyroid hormone (PTH) levels in relation to calcium supplementation. The study involved two groups of healthy, morbidly obese, premenopausal women who underwent BPD-LL. A year after the surgery, both groups had similar body weight loss. The study concluded that marked weight loss after BPD-LL results in increased bone turnover without the appearance of secondary hyperparathyroidism.

Abstract: Aim of the study was to investigate the possible mechanisms leading to stunted growth and osteoporosis in experimental arthritis. Fourty-two female rats of 7–8weeks of age were randomly assigned to three groups of 14 animals each: (a) controls; (b) adjuvant-inoculated (AA); and (c) adjuvant-inoculated rats receiving 10mg cyclosporin A (CsA) orally for 30days. Biological parameters studied were: hindpaw swelling; vertebral length progression expressed as Δ increments between days 1 and 30 as a parameter of skeletal growth, and estimation of total skeletal mineral content by dual energy X-ray absorptiometry (n =10 each group) on day 30. Endocrine parameters measured were pulsatile release of growth hormone (rGH) on day 30 following jugular cannulation and measurement of insulin-like growth factor (IGF-1) in pooled plasma from rGH profiles. Results can be summarized as follows: Untreated AA rats exhibited local signs of inflammation in comparison with controls (hindpaw diameter 8.1–8.9mm vs. 5.3–5.6mm in controls). Treatment with CsA normalized this parameter (4.9–5.6mm). Vertebral growth was significantly retarded in AA rats in comparison with controls (214±32 vs. 473±33μm; p <0.001). Administration of CsA normalized vertebral size increment with a clear tendency to overgrowth (523±43μm, n.s.). There was also a marked reduction in total skeletal mineral content in diseased (AA) rats as compared to controls (5.8±0.1 vs. 7.5±0.1g [OH-apatite]; p <0.001), and a moderate but significant increment above controls in the group receiving CsA (8.0±0.1 vs. 7.5±0.1g [OH-appatite]; p <0.04). Integrated rGH profiles exhibited a significant fall in arthritic rats and were completely restored to normal under CsA treatment. A trend toward higher rGH values was observed in the latter group (2908±554 in AA vs. 8317±1492ng/ml/240min in controls; p <0.001, and 10940±222ng/ml/240min, n.s. in the CsA group). There was a good correlation between skeletal growth and rGH pulsatility (r =0.81; p <0.001). IGF-1 followed a similar pattern (630±44 in AA vs. 752±30ng/ml in controls; p <0.04, and 769±59ng/ml in the CsA group, n.s. vs. controls). Thus, a clear tendency to skeletal overgrowth following treatment was observed in agreement with the hormonal data. It can therefore be concluded that, in experimental arthritis, attenuated GH-spiking and reduced circulating IGF-1 appear to be causally related to growth retardation, probably mimicking signs and symptoms observed in juvenile arthritis. Therapy with CsA is followed by normalization of hormonal and biological parameters accompanied by a catch up phenomenon in skeletal growth which is also observed clinically in juvenile arthritis. Generalized osteopenia is a prominent feature seemingly connected with the growth abnormalities as they parallel each other during the evolution of the disease and respond equally to therapy. [Copyright &y& Elsevier]

Abstract: Aims: Although dexamethasone (Dex) is used widely as an anti-inflammatory and immunosuppressive drug, Dex appears to have severe side-effects, including osteoporosis. This study determined the effects of Dex on duodenal and renal expressions of the calcium-processing genes transient receptor potential cation channel, subfamily V, member 5/6 (TRPV5/6), calbindin-D9k/-D28k (CaBP-9k/28k), Na+/Ca2+ exchanger 1 (NCX1), and plasma membrane Ca2+-ATPase (PMCA) 1b. Main methods: Mice were injected subcutaneously with Dex for 1 or 5 days. The mRNA and protein expression levels of these calcium-processing genes were measured by real-time PCR and immunohistochemistry/immunoblot analysis, respectively. In addition, serum parathyroid hormone (PTH) levels were measured following Dex treatments. Key findings: Treatment with Dex for 24 h resulted in the inductions of duodenal TRPV6, CaBP-9k and PMCA1b transcripts and renal TRPV5, CaBP-9k, and NCX1 transcripts, while it reduced the transcription of renal TRPV6. Although the expressional changes were weak, duodenal expressions of glucocorticoid receptor (GR), the vitamin D receptor (VDR), and renal expressions of the parathyroid hormone receptor (PTHR) and VDR were increased following 24 h treatment with Dex. A five-day treatment with Dex reduced the transcriptional levels of duodenal TRPV6 and CaBP-9k by 60%. Transcripts for VDR and GR in the duodenum increased marginally. Significance: These results suggest that the expressions of TRPV6 and CaBP-9k in the duodenum appear to be a major regulatory target for glucocorticoids (GCs), and may be involved in the negative regulation of calcium absorption in GC-induced osteoporosis (GIO). The transcriptional regulation of TRPV6 and CaBP-9k in the duodenum seems complex given that there is an increase at 1-day treatment followed by a decrease at 5-day treatment. [Copyright &y& Elsevier]

Abstract: Our recent in vitro study showed that extracorporeal shock wave (ESW) stimulated calcium deposition in human periosteal cells. In this study, we hypothesized that the use of ESW could induce new bone formation in osteoporotic bone. Using our established osteoporotic goat model, the calcaneus, distal radius and femoral condyle of the left limb were treated with ESW once per month; the contralateral side served as the control. Bone mineral density (BMD), microarchitecture and dynamic histomorphometric index were evaluated after 9 months. Trabecular BMD of the calcaneus increased significantly by 2.90%. This finding was substantiated by micro-computed tomography findings showing that trabecular bone volume fraction and trabecular thickness of the treated calcaneus were enhanced compared with the contralateral control. However, significant difference could not be detected in the other two weight-bearing skeletal sites. Mineral apposition rates of all ESW-treated regions were also consistently higher than those of the control. These findings suggest that ESW treatment could enhance local BMD by inducing new bone formation, yet the effect was more apparent in non-weight-bearing sites. (E-mail: ksleung@cuhk.edu.hk) [Copyright &y& Elsevier]

High protein intake produces an increase in net acid excretion, which in turn leads to an increase in urinary calcium. Effects of diet in urinary acid and calcium excretion depend not only on the protein content, but also may be modified by other constituents such as potassium and alkali equivalents of bicarbonate present in fruits and vegetables. Diets deficient in these potassium bases increase the acid load imposed by proteins. In consequence, diets with a high protein intake or poor in fruits and vegetables produce a low-grade systemic metabolic acidosis which exerts deleterious effects on the body, including growth retardation in children, decreased muscle and bone mass in adults, and kidney stone formation. This review intends to summarize the present evidence in relation to the effects of high protein diets in different organs and systems including hydroelectrolytic and acid base metabolism, bone metabolism, renal and endocrine function. Particular aspects that may exert a special influence in life extremes as childhood and old age are also addressed. [ABSTRACT FROM AUTHOR]