The effects of dietary changes on bone markers in postmenopausal vertebral osteopenia.

BACKGROUND & AIMS: Nutrition is one of the most important environmental factors affecting the formation of osteopenia. The purpose of this study was to investigate the effects of dietary changes on bone formation and bone resorption markers of postmenopausal women with vertebral osteopenia. METHODS: In this study, 108 women with postmenopausal vertebral osteopenia were included. Patients were observed for a month to identify their regular nutritional status. Before intervention, blood and urine samples were taken from all patients. Then, 2-day food consumption records were taken and the patients were divided into 4 groups. Different types of diets (opposite of their regular diets) were prepared for these groups (1: control, 2: reduced-carbohydrate, 3: reduced-protein, 4: reduced-sodium) and followed for 3 months. At the end of follow-ups, blood and urine samples were taken again and changes in osteocalcin (OC) and N-terminal telopeptide (NTX) levels were examined. RESULTS: According to biochemical analysis, there was a significant decrease (p < 0,001) in OC levels in reduced protein group and an increase (p > 0,05) in reduced carbohydrate group. When NTX levels were assessed, a significant decrease (p < 0.001) in the reduced carbohydrate group and a significant increase in the reduced protein group (p < 0.05) were found. CONCLUSION: Our findings show that reduced carbohydrate diet protected whereas, reduced protein diet negatively affected bone health. Osteopenic individuals were thought to be able to improve bone health and their quality of life by early dietary intervention.

Boron intake, osteocalcin polymorphism and serum level in postmenopausal osteoporosis.

The relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and osteocalcin are important in bone metabolism, however the effect of boron in bone metabolism has not been fully discovered. The study was performed on 53 postmenopausal women aged 55-60 living in parts of Balikesir, Turkey, where the subjects are naturally exposed to high (≥1 mg/L) or low (<1 mg/L) boron concentration in drinking water. 24-h urine samples were collected from all participants and creatinine clearance was detected. Boron intake levels of the subjects whose clearance levels were between 80-124 mL/min were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) in urine samples. Serum osteocalcin levels of the subjects were measured by osteocalcin enzyme-linked immunosorbent assay (ELISA) kit. Osteocalcin polymorphism rs1800247 was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum osteocalcin levels in boron-exposed postmenopausal women were significantly higher than that of control group (P ≤ 0.05) and the correlation between the serum osteocalcin level and rs1800247 polymorphism was not significant in both groups (P > 0.05). The differences in the distribution of osteocalcin genotypes and alleles in postmenopausal women were not significant between the boron exposed and the control groups (P > 0.05). Serum osteocalcin level in the CC genotype was significantly higher compared to the TC genotype in boron-exposed group (P ≤ 0.05). Our study suggests that daily boron intake of 1 mg/L may affect bone metabolism in postmenopausal women positively.

Comprehensive metabolic characterization of serum osteocalcin action in a large non-diabetic sample.

Recent research suggested a metabolic implication of osteocalcin (OCN) in e.g. insulin sensitivity or steroid production. We used an untargeted metabolomics approach by analyzing plasma and urine samples of 931 participants using mass spectrometry to reveal further metabolic actions of OCN. Several detected relations between OCN and metabolites were strongly linked to renal function, however, a number of associations remained significant after adjustment for renal function. Intermediates of proline catabolism were associated with OCN reflecting the implication in bone metabolism. The association to kynurenine points towards a pro-inflammatory state with increasing OCN. Inverse relations with intermediates of branch-chained amino acid metabolism suggest a link to energy metabolism. Finally, urinary surrogate markers of smoking highlight its adverse effect on OCN metabolism. In conclusion, the present study provides a read-out of metabolic actions of OCN. However, most of the associations were weak arguing for a limited role of OCN in whole-body metabolism.

The value of hypercalciuria in patients with osteopenia versus osteoporosis.

The aim of this study was to analyze the presence of lithogenic metabolic factors in the blood and urine of patients with osteopenia versus osteoporosis. This is a cross-sectional study including 67 patients who were divided into two groups according to the presence of either osteopenia or osteoporosis as measured by bone densitometry: group 1-40 patients with osteopenia (22 men and 18 women) and group 2-27 patients with osteoporosis (13 men and 14 women). Metabolic studies were performed on the blood and urine; statistical analysis was performed comparing means and conducting linear correlation and multivariate analyses with SPSS. Statistical significance was considered to be p ≤ 0.05. The mean age of patients in group 1 was 52.9 ± 12.8 years versus 50.3 ± 11.4 in group 2; the difference was not statistically significant. In group 2, higher levels of osteocalcin, ß-crosslaps, urinary calcium, fasting urine calcium/creatinine, 24 h urine calcium/creatinine and 24 h oxaluria were observed compared to group 1. In the multivariate analysis, only the ß-crosslaps and urinary calcium were independently associated with osteoporosis. It would be advisable to determine the urinary calcium levels in patients with osteoporosis since altered levels may necessitate modifying the diagnostic and therapeutic approach to osteoporosis.

Bone remodeling markers as lithogenic risk factors in patients with osteopenia-osteoporosis.

PURPOSE: To analyze the presence of phosphocalcic metabolism disorders in patients with osteopenia-osteoporosis without nephrolithiasis with respect to a control group. METHODS: A cross-sectional study was conducted in patients with osteopenia-osteoporosis without nephrolithiasis (n = 67) in lumbar spine or femur and in a control group (n = 61) with no lithiasis or bone disorders. Blood bone markers, phosphocalcic metabolism, fasting urine, 24-h urine lithogenic risk factors, and densitometry were recorded in both groups. SPSS 20.0 was used for statistical analysis. RESULTS: In comparison with the controls, significantly higher blood calcium (9.27 ± 0.36 vs. 9.57 ± 0.38, p = 0.0001), intact parathormone (45.6 ± 14.9 vs. 53.8 ± 18.9, p = 0.008), and alkaline phosphatase (61.9 ± 20.9 vs. 70.74 ± 18.9, p = 0.014) levels were found in patients with osteopenia-osteoporosis. In the 24-h urine test, citrate (1010.7 ± 647.8 vs. 617.6 ± 315.8, p = 0.0001) and oxalate (28.21 ± 17.65 vs. 22.11 ± 16.49, p = 0.045) levels were significantly lower in osteopenia-osteoporosis patients than in controls, with no significant difference in calcium (187.3 ± 106.9 vs. 207.06 ± 98.12, p = 0.27) or uric acid (540.7 ± 186.2 vs. 511.9 ± 167.06, p = 0.35) levels. Patients with osteopenia-osteoporosis had significantly higher levels of lithogenic risk factors associated with bone remodeling, including significantly increased ß-crosslaps and osteocalcin values and higher ß-crosslaps/osteocalcin ratios. CONCLUSION: Patients with osteopenia-osteoporosis without nephrolithiasis showed phosphocalcic metabolism disorders as well as lower urinary citrate and higher ß-crosslaps/osteocalcin and fasting calcium/creatinine ratios, which would increase the risk of nephrolithiasis. Hence, prospective studies are warranted to evaluate the long-term risks.

A High-Saturated-Fat, High-Sucrose Diet Aggravates Bone Loss in Ovariectomized Female Rats.

BACKGROUND: Estrogen deficiency in women and high-saturated fat, high-sucrose (HFS) diets have both been recognized as risk factors for metabolic syndrome. Studies on the combined actions of these 2 detrimental factors on the bone in females are limited. OBJECTIVE: We sought to determine the interactive actions of estrogen deficiency and an HFS diet on bone properties and to investigate the underlying mechanisms. METHODS: Six-month-old Sprague Dawley sham or ovariectomized (OVX) rats were pair fed the same amount of either a low-saturated-fat, low-sucrose (LFS) diet (13% fat calories; 15% sucrose calories) or an HFS diet (42% fat calories; 30% sucrose calories) for 12 wk. Blood, liver, and bone were collected for correspondent parameters measurement. RESULTS: Ovariectomy decreased bone mineral density in the tibia head (TH) by 62% and the femoral end (FE) by 49% (P < 0.0001). The HFS diet aggravated bone loss in OVX rats by an additional 41% in the TH and 37% in the FE (P < 0.05). Bone loss in the HFS-OVX rats was accompanied by increased urinary deoxypyridinoline concentrations by 28% (P < 0.05). The HFS diet induced cathepsin K by 145% but reduced osteoprotegerin mRNA expression at the FE of the HFS-sham rats by 71% (P < 0.05). Ovariectomy significantly increased peroxisome proliferator-activated receptor γ mRNA expression by 136% and 170% at the FE of the LFS- and HFS-OVX rats, respectively (P < 0.05). The HFS diet aggravated ovariectomy-induced lipid deposition and oxidative stress (OS) in rat livers (P < 0.05). Trabecular bone mineral density at the FE was negatively correlated with rat liver malondialdehyde concentrations (R(2) = 0.39; P < 0.01). CONCLUSIONS: The detrimental actions of the HFS diet and ovariectomy on bone properties in rats occurred mainly in cancellous bones and were characterized by a high degree of bone resorption and alterations in OS.

Periodontal disease exacerbates systemic ovariectomy-induced bone loss in mice.

Periodontal pathogens and/or inflammatory products from periodontitis participate in the development or progression of systemic diseases. In this context, periodontitis acts as a modifying factor to systemic health, including diabetes and cardiovascular diseases. Osteoporosis is an increasingly prevalent condition in our aging population and considered a risk factor for periodontal disease, but the effect of periodontitis on systemic bone homeostasis is unknown. We thus evaluated the effects of experimental periodontitis (EP) on systemic bone loss and the influence of estrogen deficiency in this context, using a mouse model of combined periodontitis and osteoporosis. Experimental periodontitis (EP) was induced by a ligature insertion around the mandibular first molars and Porphyromonas gingivalis infection. Three-dimensional microcomputed tomographic analyses performed 48days following infection revealed that EP and ovariectomy (OVX) induced a significantly higher femoral and mandibular bone loss compared to EP or OVX alone. EP alone did not induce systemic bone loss. In addition, the EP+OVX and EP groups showed significantly higher levels of tumor necrosis factor (TNF)-α than OVX and control groups at end point. These results suggest that periodontitis could be a risk factor for systemic bone loss, especially in post-menopausal women, and warrant further clinical investigations to confirm this association and propose adapted prophylactic and curative therapies.

Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats.

BACKGROUND/AIM: There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P - 9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). RESULTS: Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 +/- 0.2 vs 1.12 +/- 0.04 mmol/L; p < 0.001); higher mean serum phosphorus (2.42 +/- 0.46 vs 2.05 +/- 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 +/- 0.46 vs 3.05 +/- 0.58; p < 0.01) and significantly increased P1NP (489.22 +/- 46.77 vs 361.9 +/- 53.01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the contol group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 +/- 0.03 vs 1.15 +/- 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 +/- 0.13 vs 1.89 +/- 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. CONCLUSIONS: Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory.

Short-term effects of an oral contraceptive containing oestradiol valerate and dienogest on bone metabolism and bone mineral density: an observational, preliminary study.

OBJECTIVES: To evaluate the effects of a combined oral contraceptive (COC) containing dienogest/oestradiol valerate (DNG/E2V) on bone mineral density (BMD) and on serum and urinary bone turnover markers in young, healthy, fertile women. METHODS: At baseline and after three and six months of intake of the aforementioned COC, serum and urinary calcium, osteocalcin, urinary pyridinoline (PYD), and deoxypyridinoline (D-PYD) of 30 women aged 21 to 34 years were measured. At baseline and after six months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Urinary levels of PYD and D-PYD were significantly lower at three and six months in comparison with basal values (p < 0.05). Serum calcium levels showed an increasing trend, which reached statistical significance after six months in comparison with basal values while urinary levels of calcium did not vary significantly. Serum osteocalcin levels were somewhat, but not significantly, lower during pill use in comparison with basal values. After six months, spinal BMD values did not differ significantly from basal values. CONCLUSIONS: The DNG/E2V COC has no short-term adverse effect on bone turnover markers. No significant change in BMD was observed after six months of use of that pill.

Tactile/kinesthetic stimulation (TKS) increases tibial speed of sound and urinary osteocalcin (U-MidOC and unOC) in premature infants (29-32weeks PMA).

Preterm delivery (<37 weeks post-menstrual age) is associated with suboptimal bone mass. We hypothesized that tactile/kinesthetic stimulation (TKS), a form of infant massage that incorporates kinesthetic movement, would increase bone strength and markers of bone accretion in preterm infants. Preterm, AGA infants (29-32 weeks) were randomly assigned to TKS (N=20) or Control (N=20). Twice daily TKS was provided 6 days per week for 2 weeks. Control infants received the same care without TKS treatment. Treatment was masked to parents, health care providers, and study personnel. Baseline and week two measures were collected for tibial speed of sound (tSOS, m/sec), a surrogate for bone strength, by quantitative ultrasound (Sunlight8000) and urine markers of bone metabolism, pyridinium crosslinks and osteocalcin (U-MidOC and unOC). Infant characteristics at birth and study entry as well as energy/nutrient intake were similar between TKS and Control. TKS intervention attenuated the decrease in tSOS observed in Control infants (p<0.05). Urinary pyridinium crosslinks decreased over time in both TKS and CTL (p<0.005). TKS infants experienced greater increases in urinary osteocalcin (U-MidOC, p<0.001 and unOC, p<0.05). We conclude that TKS improves bone strength in premature infants by attenuating the decrease that normally follows preterm birth. Further, biomarkers of bone metabolism suggest a modification in bone turnover in TKS infants in favor of bone accretion. Taken together, we speculate that TKS improves bone mineralization.

Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants.

Preterm (PT) infants are at risk of growth failure despite advanced early care and nutrition. In addition to poor weight gain, slow postnatal linear growth also is associated with adverse neurological outcome. Markers distinguishing infants at risk for impaired catch-up growth are needed. The aim of this longitudinal study was to determine the extent to which postnatal levels of circulating cartilage (serum pro-C-type natriuretic peptide [S-proCNP]) and urinary bone metabolic markers (urinary osteocalcin [MidOC] and two forms of C-terminal cross-linked telopeptide of type I collagen [U-α-CTX-I and U-ß-CTX-I]) predict catch-up growth in infancy in 67 PT and 58 full-term (FT) infants. PT infants were significantly shorter than FT infants during the first 6 months of life, but no statistically significant difference was found at the corrected age of 14 months (M14). At the age of 3 months (M3), S-ProCNP and U-MidOC levels, but not U-α-CTX-I and U-ß-CTX-I levels, correlated positively with prospective growth velocity from M3 to M14 (ρ = 0.460, p < 0.001 and ρ = 0.710, p < 0.001, respectively). In predicting slow linear growth (growth velocity at the lowest quartile), the area under the S-ProCNP ROC curve was 0.662 and that of U-MidOC 0.891. Thus, U-MidOC, and to lesser extent S-ProCNP at M3 are predictors of catch-up growth in infancy.

The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants.

OBJECTIVES: This study evaluated the influence of oestrogen deficiency and its therapies on bone tissue around osseointegrated implants. METHODS: Implants were placed in 66 female rats tibiae. The animals were assigned into five groups: control (CTL), sham, ovariectomy (OVX), oestrogen (EST), and alendronate (ALE). While CTL was sacrificed 60 days after implant placement, other groups were subjected to ovariectomy or sham surgery according to group and euthanized after 90 days. Blood and urine samples were collected at sacrifice day for osteocalcin (OCN) and deoxypyridinoline (DPD) quantification. Densitometry of femur and lumbar vertebrae was performed in order to evaluate rats' skeletal impairment. Non-decalcified sections were referred to fluorescent and light microscopy for analyses of mineral apposition rate (MAR), eroded and osteoclastic surfaces, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO). RESULTS: Results from the OVX group showed significantly lower bone mineral density (BMD), BIC, BAFO, and MAR, while OCN, deoxipiridinoline, eroded surface and ostecoclastic surface were increased compared with the other groups of the study. ALE reduced OCN and DPD concentrations, MAR, osteoclastic and eroded surfaces, and no difference was in BIC and BAFO relative to SHAM. EST and CTL showed similar results to SHAM for measurements. CONCLUSIONS: Oestrogen deficiency exerted a negative influence on bone tissue around implants, while oestrogen replacement therapy and alendronate were effective against its effects. Although alendronate therapy maintained the quantity of bone around implants, studies evaluating bone turnover kinetics are warranted.

[State of bone structures in children with acute leukemia, experiencing unfavorable factors from Chernobyl accident].

The authors present an assessment of bone structure condition in children with acute leukemia. The changes in the collagen molecule, amino acid composition of urine and proteins reparation processes were revealed. Calcium phosphate excretion in the patients urine were increased. The serum osteocalcin level and colony formation efficiency of bone marrow fibroblasts in acute leukemia patients are lower than in control group. In the initial period of the disease 32% of patients have disturbancies in their endocrine status. The bone structure violation is combined with unfavorable disease outcome. The effectiveness of the treatment and prevention steps in acute leukemia patients depends on the leukemic process stage.

The effects of a walking exercise program on fall-related fitness, bone metabolism, and fall-related psychological factors in elderly women.

The purpose of this study was to determine the effects of a 3-month walking exercise program with ankle weights on fall-related fitness, bone metabolism, and fall-related psychological factors. Fall-related fitness was determined from strength, balance, agility, aerobic endurance, muscle mass, and fat mass measures. Bone metabolism was measured using bone density, hormones, and biochemical markers. Fall-related psychological factors included fear of falling and falls efficacy. A 2 × 2 factorial with repeated measures design was used. All subjects were community-dwelling elderly women who volunteered to participate, and randomly were assigned to either an exercise group (n = 11) or a control group (n = 10). Results revealed significant changes in upper body strength, leg strength, aerobic endurance, and body composition. Additionally, hormones and biochemical markers changed significantly over time. Trunk fat and fear of falling changed differently among the two groups. In conclusion, this study suggests that a 3-month walking exercise program with ankle weights may have positive effects on fall-related fitness, bone metabolism, and fall-related psychological factors.

Sustained activation of renal N-methyl-D-aspartate receptors decreases vitamin D synthesis: a possible role for glutamate on the onset of secondary HPT.

N-methyl-D-aspartate (NMDA) receptors (NMDAR) are tetrameric amino acid receptors that act as membrane calcium channels. The presence of the receptor has been detected in the principal organs responsible for calcium homeostasis (kidney, bone, and parathyroid gland), pointing to a possible role in mineral metabolism. The aim of this study was to test the effect of NMDAR activation in the kidney and on 1,25(OH)2D3 synthesis. We determined the presence of NMDAR subunits in HK-2 (human kidney cells) cells and proved its functionality. NMDA treatment for 4 days induced a decrease in 1α-hydroxylase levels and 1,25(OH)2D3 synthesis through the activation of the MAPK/ERK pathway in HK-2 cells. In vivo administration of NMDA for 4 days also caused a decrease in blood 1,25(OH)2D3 levels in healthy animals and an increase in blood PTH levels. This increase in PTH induced a decrease in the urinary excretion of calcium and an increase in urinary excretion of phosphorous and sodium as well as in diuresis. Bone turnover markers also increased. Animals with 5/6 nephrectomy showed low levels of renal 1α-hydroxylase as well as high levels of renal glutamate compared with healthy animals. In conclusion, NMDAR activation in the kidney causes a decrease in 1,25(OH)2D3 synthesis, which induces an increase on PTH synthesis and release. In animals with chronic kidney disease, high renal levels of glutamate could be involved in the downregulation of 1α-hydroxylase expression.

Biochemical markers of particle induced osteolysis in C57BL/6 mice.

BACKGROUND: Micro-structural changes associated with ultra high molecular weight polyethylene particle (UHMWPE) induced osteolysis, the most frequent cause of aseptic loosening, have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography. However, little is known regarding the serological changes that occur during this process. METHODS: Serological parameters for bone metabolism [calcium, phosphate, osteocalcin (OCN), deoxypyridinoline (DPD)/creatinine, alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor-κB] were analyzed in this animal model for particle induced osteolysis. Ten C57BL/6 mice were divided at random into sham operated and UHM-WPE implanted groups. Blood and urine samples were collected prior to and at 14 days after surgery. RESULTS: Implantation of UHMWPE lead to a significant decrease in bone volume (p=0.027). Both groups (sham/UHMWPE) showed a significant increase in calcium (p=0.004/p=0.027) and phosphate (p=0.001/p=0.001), without correlation to particle implantation. Significantly higher concentrations of DPD/creatinine (p=0.034) and OCN (p=0.022) were found after implantation of UHM-WPE. In addition, parameters could not be correlated to particle induced osteolysis. CONCLUSIONS: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.

Changes in bone mineral density and bone metabolism markers in premenopausal women with multiple sclerosis and the relationship to clinical variables.

Bone mineral density (BMD) is affected in young adults with multiple sclerosis (MS), which leads to disabling disease. We aimed to show changes that were independent of immobilization by measuring BMD and laboratory markers of bone metabolism in mobile MS patients. We compared a total of 52 premenopausal female patients with relapsing-remitting multiple sclerosis (RRMS) to 41 women of similar age who had no risk factors for osteoporosis. The lumbar and femur BMD were measured using the dual energy X-ray absorptiometry (DXA) method. The urine concentration of serum 25-hydroxycholecalciferol (25-OH vit D(3)), and pyridinoline and deoxypyridinoline were also measured. The concentration of serum osteocalcin was measured to determine the speed of bone metabolism. The mean age of patients (+/- standard deviation [SD]) was 36.1+/-7.4. The average Expanded Disability Status Scale (EDSS) score was 2.2+/-1.8. The concentration of 25-OH vit D(3) and osteocalcin was lower, whereas the concentration of parathyroid hormone (PTH), alkaline phosphatase (ALP), pyridinoline and deoxypyridinoline was higher in the patient group. In the patient group, lumbar 2-4 BMD, T score and Z score and femur neck and trochantor BMD, T score and Z score were significantly lower than in the control group. There was a significant negative relationship between: the disease period and L 2-4 BMD, T score and Z scores; and the femoral neck BMD, T score and Z scores. There was a significant relationship between the total Functional Independence Measure score and the femoral neck, femoral trochanter BMD, T score, and Z score. There was a significant negative relationship between the average EDSS, L 2-4 and all the DXA measurements obtained from the femur. There was a significant relationship between the 25-OH vit D(3) concentration and L 2-4 T score and Z score from the DXA measurements obtained from the femur. There were no significant relationships between osteocalcin, pyridinoline, deoxypyridinoline levels and the BMD measurements. Therefore, the duration of the disease and decrease in functional capacity are the main factors that affect BMD in MS. Apart from the decrease in functional capacity, 25-OH vit D(3) deficiency and secondary PTH increase contribute to the BDM changes observed in MS.

[Progress in the treatment of osteoporosis].

The purpose of the treatment of osteoporosis is to reduce fracture risk and maintain/improve quality of life (QOL). The criteria for initiating pharmacotherapy to prevent fragility fractures should be provided separately from the criteria for diagnosis of osteoporosis. In Japan, low bone mineral density (BMD), prevalent fracture, and age are established as fracture risk factors from available data. A meta-analysis conducted by the WHO assured that excessive drinking (2 units a day or more), current smoking, and a family history of hip fracture are fracture risk factors. Moreover, in WHO technical report 921, high levels of CTX, a bone resorption marker as well as uncarboxylated osteocalcin were cited as risk factors of hip fracture, which can be measured in medical practice in Japan. Pharmacotherapy should be initiated with the consideration of the above risk factors. Recent large scale of randomized control trial(RCT), followed by meta-analysis demonstrated that bisphosphonates such as alendronate and risedronate as well as raloxifene (selective estrogen receptor modulator) are top grade of drugs which prevent fragility fracture in osteoporotic patients. Now, it is possible to perform evidence-based medicine in daily medical practice. As for secondary osteoporosis, along with treatment of underlying diseases, treatment aimed at preventing bone loss is necessary in many cases. Accumulating evidence is available about increased fracture threshold in glucocorticoid- and diabetes mellitus-induced osteoporosis. Therefore, early treatment should be appropriate in these cases. In osteoporotic patients, atherosclerotic vascular calcification as well as abnormal lipid metabolism often coexists. Multiple vertebral fractures followed by kyphosis often causes functional disorders of the digestive and respiratory systems.

Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial.

OBJECTIVE: To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. METHODS: In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. RESULTS: One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. CONCLUSION: Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.

Urinary osteocalcin and other markers of bone metabolism: the effect of risedronate therapy.

OBJECTIVE: Serum osteocalcin (S-OC) is widely used as an index of bone formation. However, there is evidence that some urinary fragments of OC reflect resorption and might be useful in monitoring antiresorptive therapy. Here, we report 6-month changes in urinary midfragments of osteocalcin (U-MidOC) and other bone turnover markers in response to risedronate treatment. MATERIAL AND METHODS: The study group comprised 19 patients with postmenopausal osteoporosis, aged 49-66 years, and receiving risedronate therapy. Fifty-four premenopausal women served as controls. Osteoporosis was diagnosed by lumbal bone mineral density (BMD). Urinary osteocalcin was measured by the U-MidOC assay for midfragments. Bone formation was assessed by S-PINP and S-OC, and resorption by S-CTx-I. RESULTS: At baseline, U-MidOC was significantly correlated only with S-OC. After the 1st month of therapy, a similar decrease was observed in the values of U-MidOC and S-CTx-I, but in formation markers S-P1NP and S-OC only after three months. The rapid decrease in U-MidOC, analogous to S-CTX-I, and the different kinetics for urinary and serum OC suggest that urinary OC midfragments are more associated with resorption than S-OC. An association was also observed between the 1-month change in U-MidOC and 12-month gain in lumbar BMD. The response in U-MidOC after only the 1st month of therapy makes it a potential marker for monitoring the effect of risedronate, presumably reflecting different aspects of bone resorption than S-CTx-I does.