BONE MASS RECOVERY OF OSTEOPENIC VITAMIN D INSUFFICIENT RATS FROM STRONTIUM RANELATE TREATMENT: DOES THE RESPONSE DEPEND ON VITAMIN D NUTRITIONAL STATUS OR ON SOURCE OF VITAMIN D (D2 VERSUS D3)?

2010 ◽  
Vol 13 (03) ◽  
pp. 95-108
Author(s):  
Macarena M. S. Gonzales Chaves ◽  
Clarisa Marote ◽  
Gretel G. Pellegrini ◽  
Andrés Pighin ◽  
Maria C. de Landeta ◽  
...  

It was investigated if Vitamin D (Vit D) status or source (Vitamin D2 vs. Vitamin D3) interferes with bone mass recovery from strontium ranelate (SrRa) treatment of rats with Vit D insufficiency and established osteopenia. Osteopenic and Vit D insufficient rats were divided in groups to complete a 105-day period. First experiment: The rats were fed with diets that only varied in Vit D (100 vs. 0 IU%) and/or SrRa (0 vs. 900 mg/kg/day) content. A SHAM group received Vit D throughout the experience. Second experiment: Rats were divided into groups and received Vit D2 or Vit D3 through diet and SrRa by gavages in a fasting state. Two SHAM groups received Vit D2 or Vit D3 throughout the study. Results: Levels of 25-hydroxyvitamin 25OHD were reduced in groups lacking dietary Vit D (p < 0.001). Independently of Vit D status or source, SrRa did not affect body weight gain or bone alkaline phosphatase levels; osteocalcin and C-terminal telopeptide of type I collagen levels were reduced (p < 0.05) and bone Sr content was increased (p < 0.0001). Although no improvement in biomechanical parameters was observed, total skeletal bone mineral content and proximal tibial bone mineral density were increased (p < 0.05). There was a reduction in the trabecular number and an increase in the trabecular surface and bone volume without reaching SHAM levels. Conclusion: This is the first study that examined SrRa effects in an osteopenic vitamin D–insufficient experimental model. Under our experimental conditions, SrRa increased bone Sr content independently of Vit D status or source; however, no evidence of an anabolic or antifracture effect was found, and only a slight decrease in some bone resorption parameters was observed.

2018 ◽  
Vol 18 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Mehmet Dagli ◽  
Ali Kutlucan ◽  
Sedat Abusoglu ◽  
Abdulkadir Basturk ◽  
Mehmet Sozen ◽  
...  

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.


2020 ◽  
Vol 26 (12) ◽  
pp. 1477-1485
Author(s):  
Wen-bin Zheng ◽  
Yi Dai ◽  
Jing Hu ◽  
Di-chen Zhao ◽  
Ou Wang ◽  
...  

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD. Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated. Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group ( P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline). Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol. Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1749.2-1749
Author(s):  
A. Catalano ◽  
F. Bellone ◽  
A. Gaudio ◽  
M. C. Sottile ◽  
S. A. Stoian ◽  
...  

Background:Vitamin D repletion is known to maximize the response to bisphosphonates (BPs) in terms of both bone mineral density (BMD) changes and anti-fracture efficacy. The contribute of vitamin to BMD after discontinuation of BPs has been poorly investigated.Objectives:To explore whether change of vitamin D status may contribute to the tail effect of alendronate (ALE) on BMD.Methods:Participants in this retrospective study were postmenopausal osteoporotic women exposed to ALE. Either cholecalciferol or calcifediol have been administered, as vitamin D supplementation in accordance to good clinical practice, during ALE treatment and after ALE discontinuation. BMD was evaluated by Dual-energy X-ray absorptiometry (DXA) at lumbar spine and femoral site. Vitamin D status has been checked by measuring 25(OH)D serum levels through HPLC. Surrogate bone formation and resorption markers (i.e. C-terminal telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP), respectively) were also evaluated. The Fracture Risk Assessment Tool (FRAX) served to estimate the participants’ 10-year fracture risk for major osteoporotic and hip fracture.Results:88 postmenopausal osteoporotic women (age 61.14 ± 6.96 yr.) were included in the final analysis. The 10-year probability of major and hip fractures was 18.31±11.51 and 8.60 ± 10.55 %, respectively. Participants were exposed to ALE treatment for 31.27 ± 20.69 months; then they stopped treatment for 33.33 ± 18.97 months. Change of BMD was inversely related to drug holiday (r=-0.27, p=0.005). Modification of 25(OH)D was inversely associated with change of ALP (r=-0.22, p=0.018) and CTX levels (r=-0.3, p=0.06). By distributing participants in tertiles according to variation of 25(OH)D levels over time, women allocated in the tertile with the higher increase of 25(OH)D showed a 5.7% BMD gain that was two times larger in comparison with participants with lower increase of 25(OH)D. At a multiple regression analysis, after correcting for ALE treatment duration, bone turn-over marker modifications, BMI and age at menopause, BMD change at lumbar spine was significantly associated with time since menopause (ß=2.28, SE 0.44, p<0.0001), FRAX score (ß=-0.65, SE 0.29, p=0.03), drug holiday duration (ß=-2.17, SE 0.27, p<0.0001) and change of 25(OH)D levels (ß=0.15 SE 0.03, p=0.0007).Conclusion:After ALE discontinuation, modification of BMD are strictly associated with change of vitamin D status.Disclosure of Interests:None declared


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Elizabeth M Curtis ◽  
Rebecca J Moon ◽  
Stefania D'Angelo ◽  
Sarah R Crozier ◽  
Nicholas J Bishop ◽  
...  

Abstract Background Observational studies have demonstrated associations between maternal gestational vitamin D status and offspring bone health. We have recently shown, in a randomised controlled trial, that pregnancy vitamin D supplementation leads to improved offspring bone mass at birth amongst winter deliveries (when background 25(OH)-vitamin D levels are lowest). In the present analysis, we aimed to evaluate whether the beneficial effect of pregnancy vitamin D supplementation on neonatal bone mass is sustained into early childhood, with bone indices assessed at age 4 years in a subset of participants of the MAVIDOS trial. Methods Pregnant women were randomised in Southampton, Oxford and Sheffield, in a double-blind design, to 1000 IU/day cholecalciferol or matched placebo from 14 weeks’ gestation to birth. At 4 years of age (Southampton participants only, n = 723 births), offspring assessments included anthropometry, whole-body dual-energy x-ray absorptiometry (DXA) [Hologic Horizon, yielding whole body less head (WBLH) bone mineral content (BMC), bone mineral density (BMD), bone area (BA) and lean mass (LM)], and a maternal questionnaire. Linear regression was used to estimate the mean difference (represented by β) in outcomes between the two randomisation arms, adjusted for sex and age at DXA. Further models were additionally adjusted for gestational age, maternal BMI, and child’s sedentary time. All outcomes were standardised to a standard deviation scale, for ease of comparison. Full ethics and MHRA approvals were granted. Results 564 children attended the 4-year visit; 452 had a useable DXA with minimal movement artefact. Maternal pregnancy vitamin D supplementation led to greater offspring indices of bone mass compared with placebo, irrespective of season. For example, WBLH BMD at age 4 years was greater in the offspring of supplemented mothers [β = 0.18 SD (95%CI: 0.00, 0.35), p = 0.047]; there was also evidence of greater LM in the intervention group [β = 0.15 SD (95%CI: -0.02, 0.31), p = 0.081]. In fully adjusted models associations were consistent for lumbar spine indices and for BA and BMC. In keeping with the offspring findings, maternal vitamin D supplementation led to significantly higher maternal plasma 25(OH)D concentrations in late pregnancy (34 weeks’ gestation): placebo group (median(IQR)): 42.4 nmol/l (23.3, 56.4); vitamin D group: 67.4 nmol/l (56.2, 80.3); p &lt; 0.001. Conclusion This is the first ever demonstration in a large placebo-controlled, double-blind randomised controlled trial that maternal pregnancy vitamin D supplementation leads to improved bone and lean mass in children. Our findings suggest that maternal cholecalciferol supplementation may have lasting benefits for offspring musculoskeletal health and thus represent an important public health message. This work was supported by grants from Versus Arthritis 17702, Medical Research Council (MRC #405050259; #U105960371), Bupa Foundation, NIHR Southampton Biomedical Research Centre (BRC), University of Southampton, and NIHR Oxford BRC, University of Oxford. EC was supported by the Wellcome Trust (#201268/Z/16/Z). Disclosures E.M. Curtis None. R.J. Moon None. S. D'Angelo None. S.R. Crozier None. N.J. Bishop None. S. Gopal- Kothandapani None. S. Kennedy None. A.T. Papageorghiou None. R. Fraser None. S.V. Gandhi None. I. Schoenmakers None. A. Prentice None. H.M. Inskip None. K.M. Godfrey None. K. Javaid None. R. Eastell None. C. Cooper None. N.C. Harvey None.


2019 ◽  
Vol 25 (14) ◽  
pp. 1653-1662
Author(s):  
Junjie Wang ◽  
Hongzhuo Li

Background: Glucocorticoid (GC)-induced osteoporosis and fractures have become a serious problem for Eastern Asians. Bisphosphonates (BPs), vitamin D and a combination treatment are effective methods to prevent and treat GC-induced osteoporosis. Objective: The study aimed to compare the efficacy of BPs, vitamin D and a combination treatment for preventing and managing GC-induced osteoporosis in Eastern Asians. Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane CENTRAL databases was undertaken for randomized controlled trials (RCTs) on the effect of BPs, vitamin D and the combination treatment on GCs-induced osteoporosis in Eastern Asian populations. Primary outcome measures were the change in bone mineral density (BMD) and bone turnover markers. The final search was performed in March 2019. Results: Nine RCTs were included. A total of 545 patients met the inclusion criteria. Compared with vitamin D, BPs and the combination treatment significantly alleviated osteoporosis of the spine and femoral neck in Eastern Asians with GC-induced osteoporosis. At the same time, the change in serum bone-specific alkaline phosphatase (BAP) and serum C-telopeptide of type I collagen (CTX) levels was observed to be significantly less with BPs and the combination treatment with vitamin D alone. No significant difference was found between BPs and the combination treatment in the markers mentioned above. Conclusion: Compared with vitamin D alone, BPs alone and the combination treatment were significantly effective on Eastern Asians with GC-induced osteoporosis. Compared with the combination treatment, BPs alone were observed to be effective enough to increase the BMDs of the spine and femoral neck on both sides and thus prevent GC-induced osteoporosis in Eastern Asians.


Author(s):  
Kusworini Handono ◽  
BP Putra Suryana ◽  
Sulistyorini Sulistyorini

Rheumatoid Arthritis (RA) is a systemic autoimmune disease accompanied by decreasing bone mass density and ultimately leads toosteoporosis. The cause of decreased bone mass density is still unknown, but the inflammation has been suspected as an important factor.The correlation between the severity of inflammation with the decrease in bone mass density in Indonesian RA patients has not been muchstudied. The purpose of this study was to know the assessment in the correlation between levels of C-reactive protein (CRP), Tumour NecrosisFactor-α (TNFα) and bone mineral density (BMD) with bone resorption marker CTx-1 β-Cross Laps in premenopausal RA patients.Thisobservational study using cross sectional design, was carried out in the Rheumatology Clinic and Central Laboratory of RSSA, Malang fromAugust 2009 until October 2010. All 47 RA patients were diagnosed according to revised of the 1997 American College of Rheumatology(ACR). Measurement of CRP levels uses turbidimetry method, TNF-α and CTX-1 β-Cross Laps levels using ELISA methods and the measurementof BMD using DEXA. The results of this study showed mean levels of CRP were 4.288±1.775 g/L, TNF-α were 322.077±275.248 pg/mLand CTX-1 β-Cross Laps were 0.588±0.139 ng mL. The correlation of CRP and TNF-α levels with CTX-1 β-Cross Laps level were r=0.5832,p=0.453 and r=0.615, p=0.041. Correlation of CTX-1 β-Cross Laps level and Femoral Neck BMD was r=–0.469, p=0.143 and r=0.248,p=0.799 for L average BMD. There was no correlation between CRP level and BMD results with bone resorption marker CTX-1 β-Cross Laps,but there is a significant correlation between high levels of TNFα with CTX-1 β-Cross Laps. It seems that TNF-α appears to be contributed tothe decrease of bone mass density in RA patients.


2016 ◽  
Vol 50 (4) ◽  
pp. 421
Author(s):  
Zhan-Jun Shi ◽  
Jian-Ping Lin ◽  
Ning-Jiang Shen ◽  
Jian Wang ◽  
Zao-Min Li ◽  
...  

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,


Medicina ◽  
2013 ◽  
Vol 49 (4) ◽  
pp. 28 ◽  
Author(s):  
Pavel Marozik ◽  
Irma Mosse ◽  
Vidmantas Alekna ◽  
Ema Rudenko ◽  
Marija Tamulaitienė ◽  
...  

Background and Objective. Variation of osteoporosis in the population is the result of an interaction between the genotype and the environment, and the genetic causes of osteoporosis are being widely investigated. The aim of this study was to analyze the association between the polymorphisms of the vitamin D receptor (VDR), type I collagen (COL1A1), and lactase (LCT) genes and severe postmenopausal osteoporosis as well as bone mineral density (BMD). Material and Methods. A total of 54 women with severe postmenopausal osteoporosis and 77 controls (mean age, 58.3 years [SD, 6.2] and 56.7 years [SD, 7.42], respectively) were included into the study. The subjects were recruited at the City Center for Osteoporosis Prevention (Minsk, Belarus). Dual-energy x-ray absorptiometry was used to measure bone mineral density at the lumbar spine and the femoral neck. Severe osteoporosis was diagnosed in the women with the clinical diagnosis of postmenopausal osteoporosis and at least 1 fragility fracture. The control group included women without osteoporosis. Polymorphic sites in osteoporosis predisposition genes (ApaI, BsmI, TaqI, and Cdx2 of the VDR gene, G2046T of the COL1A1 gene, and T-13910C of the LCT gene) were determined using the polymerase chain reaction on the deoxyribonucleic acid isolated from dried bloodspots. Results. The data showed that the ApaI and BsmI polymorphisms of the VDR gene and T- 13910C of the LCT gene were associated with severe postmenopausal osteoporosis in the analyzed Belarusian women (P<0.01). A statistically significant positive correlation between the VDR risk genotypes ApaI and TaqI and bone mineral density was found (P<0.05). Conclusions. The findings of this study suggest that at least the ApaI and BsmI polymorphisms of the VDR gene and T-13910C of the LCT gene are associated with the risk of postmenopausal osteoporosis in our sample of the Belarusian women.


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e028129 ◽  
Author(s):  
Jing Wang ◽  
Lin Chen ◽  
Yan Zhang ◽  
Chen-guang Li ◽  
Hao Zhang ◽  
...  

ObjectiveTo determine the relationship between serum vitamin B6(Vit B6) concentration and the status of bone mineral density and identify the relationship between serum Vit B6 and bone metabolism parameters in middle-aged and older people in China.DesignThe present study was a cross-sectional study within the framework of an ongoing prospective population-based cohort study.Setting and participantsA total of 1829 residents (men ≥50 years and women ≥45 years) from two subdistricts were recruited from July 2015 to February 2016 in Shanghai, China.MeasuresRecruited residents were grouped (control, osteopenia and osteoporosis) according to their lumbar spine bone mineral density, measured through dual-energy X-ray absorptiometry. Serum Vit B6concentrations, bone turnover marker concentrations and calcium and phosphorus metabolism parameters were assessed.ResultsNo significant linear trend between serum Vit B6concentrations and lumbar bone mass was observed in the men. In the women, the average osteoporosis risk was 61% higher at serum Vit B6concentrations of <19.2 μg/L than at those of >26.9 μg/L (OR 1.61, 95% CI 1.00 to 2.58). However, there was no significance after controlling of serum 25-hydroxy-vitamin D concentration and parathyroid hormone concentration, respectively. In the osteoporotic women, the serum Vit B6concentration was significantly negatively correlated to concentrations of bone turnover marker including N-terminal propeptide of type I collagen, β-C-terminal telopeptide of type I collagen and osteocalcin. It was also positively related to the serum 25-hydroxy-vitamin D concentration and inversely related to the serum parathyroid hormone concentration.ConclusionsA relatively low serum Vit B6concentration, even in the normal range, may be a risk factor for osteoporosis in postmenopausal women, which is dependent on serum 25-hydroxy-vitamin D concentration and parathyroid hormone concentration.Trial registration numberNCT02958020; Post-results.


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