Decreased Bone Mineral Content Research Articles

OR13-01 Type 1 Diabetes Is Associated With Differential Skeletal Effects At The Onset Of Peak Bone Accrual

Abstract Disclosure: A.V. Brossfield: None. K.M. Williams: None. A.B. Sopher: None. D.J. McMahon: None. J. Fernando: None. S. Agarwal: None. M.R. Rubin: None. Objective: Type 1 diabetes (T1D) often develops prior to attainment of peak bone mass, yet few data exist regarding bone accretion in the peri-pubertal period. We hypothesized that T1D have disrupted bone architecture at the onset of peak bone mass accrual in association with hyperglycemia and advanced glycation endproduct (AGE) accumulation. Methods: We enrolled T1D and controls at onset of peak bone accretion (Tanner: girls 2/3, boys 3/4) and assessed aBMD by DXA and volumetric BMD (vBMD), microarchitecture, and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT) with finite element analysis (µFE) at the distal (4%) and proximal (30%) radius and tibia. We assessed time in hyperglycemia (>180 mg/dL) by continuous glucose monitoring and AGE accumulation by skin autofluorescence (SAF). Results: T1D (n=29, age 12.5 ± 0.3 [SE] yr, 79% male, 68% white) vs controls (n=31, 12.2 ± 0.3 yr, 55% male, 68% white) had higher BMI (21.3 ± 1 vs 18.4 ± 0.5 kg/m2; p=0.04), fasting glucose (168.5 ± 9 vs 88.4 ± 2 mg/dL; p<0.0001) and HbA1c (8.4 ± 0.8 vs 5.0 ± 0.2%; p=0.05) with a trend toward higher bone age (13.5 ± 0.3 vs 12.6 ± 0.3 yr, p=0.07) and lower 25OHD (24.0 ± 1 vs 34.8 ± 3 ng/mL, p=0.08). After multivariate adjustment (sex, bone age, height and weight), DXA showed decreased bone area in T1D at the total, sub-total, leg, rib and ultradistal radius, and decreased bone mineral content at the rib, leg and trochanter (ranging from -4.1% to -13.5%, all p <0.05). Multivariate adjusted HRpQCT data showed decreased trabecular area in T1D at the distal radius (169.9 ± 8 vs 201.2 ± 8 mm2; p=0.007) and tibia (578 ± 17 vs 631 ± 17 mm2; p=0.04) and decreased cortical perimeter at the distal radius (56.0 ± 1 vs 60.1 ± 1 mm2; p=0.009). However, T1D had increased cortical vBMD at the distal (698.2 ± 8 vs 663.5 ± 8 mg HA/cm3; p=0.004) and proximal radius (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and tibia (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and increased cortical thickness at the distal radius (0.74 ± 0.03 vs 0.64 ± 0.03 mm; p=0.03). There was no difference in bone strength by µFE. Within T1D, lower trabecular area at the distal radius was associated with higher SAF (β -69.26 ± 30 mm2; p=0.04) while higher cortical vBMD at the distal tibia was associated with higher time in hyperglycemia (β 0.633 ± 0.3 mg HA/cm3; p=0.03). Conclusion: T1D at the onset of peak bone accrual have decreased bone area and mineral content by DXA. They also have decreased trabecular area but increased cortical vBMD by HRpQCT, in association with AGE accumulation and hyperglycemia. We speculate that reduced bone turnover with hyperglycemia might lead to reduced area at more metabolically active trabecular sites but is compensated for by excess mineral accumulation at less active cortical sites, with overall maintenance of bone strength. Follow up will elucidate progression of these alterations during the growth spurt. Presentation: Friday, June 16, 2023

Physiochemical Dissolution Governs Early Modifications in Acid-Exposed Murine Bone with Long-term Recovery

Metabolic acidosis (MA), a disease affecting millions annually, is clinically characterized by a decrease in systemic pH and bicarbonate. MA has been shown to have skeletal consequences, such as increased bone loss and fractures. However, the mechanisms impacting the mechanics of bone remain unknown. To determine this, we characterized the skeletal phenotypes resulting from two independent regimes of ammonium chloride (NH4Cl) acid-dosing in skeletally mature CD-1 mice for 1, 3, 7, and 14 days to establish the temporal progression of materials-level skeletal defects. The classical, flat-dose model resulted in a temporary decrease in blood pH but did not reduce blood bicarbonate levels. Minimal alterations were observed in bone composition, structure, mechanics, and cellular behavior. However, the graded administration of NH4Cl maintained MA for up to 14 days. This resulted in decreased bone mineral content, collagen organization, and bone volume while increasing mineral crystallinity at early time points followed by a return to baseline. Changes to the matrix lead to a potential decrease in bone toughness at early time points, which may explain the increased fracture risk seen clinically. However, there were no changes in bone formation rate nor osteoclast number or activity during any time point. After 14 days, the bones were fully recovered even though the mice were still under acidotic conditions. Ultimately, we conclude that physicochemical dissolution is the main mechanism for early changes in murine bone, which is influenced by the dosing of exogenous acid loading. This knowledge will aid the discovery of treatments that prevent acidosis-induced bone dissolution.

A Review of Three Decades of Research Dedicated to Making Equine Bones Stronger: Implications for Horses and Humans

Much research has been conducted in an attempt to decrease skeletal injuries in athletic horses. The objective of this literature review is to compile the findings of over three decades of research in this area, make practical recommendations, and describe how research can develop over the years. An initial study investigating the role of bioavailable silicon in the diets of horses in race training produced the unexpected finding of decreased bone mineral content of the third metacarpus subsequent to the onset of training. Further studies revealed this decrease to be associated with stall housing eliminating high-speed exercise, leading to disuse osteopenia. Only relatively short sprints (between 50 and 82 m) were necessary to maintain bone strength and as few as one sprint per week provided the needed stimuli. Endurance exercise without speed fails to elicit the same benefits to bone. Proper nutrition is also required for optimal bone health, but without the right exercise, strong bone cannot be maintained. Several pharmaceuticals may have unintended consequences capable of impairing bone health. Many of the factors influencing bone health in horses also exist in humans including a sedentary lifestyle, improper nutrition, and pharmaceutical side-effects.

Comparison of quantitative ultrasonography and dual X-ray absorptiometry for bone status assessment in South African children living with HIV.

Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.

Influences on Skeletal Health and Bone Mineralization in Children.

Bone is in its most active formation phase of mineralization in the pediatric and adolescent population. Peak bone mass is achieved around the late teens to early 20s. Deficient bone mineralization and decreased peak bone mass acquisition predispose an individual to childhood fractures or lifelong fracture risk. Adolescent fragility or stress fractures should prompt a secondary evaluation for the causes of a low bone mineral content, the root of a fracture. The purpose of this article is to review published literature that discusses the risk factors associated with a decreased bone mineral content in children from birth to the age of peak bone mass. The article also includes a public health planning model for pediatric osteoporosis.

Effect of 2-6 weeks of systemic steroids on bone mineral density in children.

Background The use of systemic steroids for 6+ weeks in children is associated with decreased bone mineral content (BMC) and density (BMD). However, the effects of a shorter duration of use on BMD are unknown.Purpose To determine the effect of the use of systemic steroids for 2–6 weeks on BMD and BMC in pediatric patients.Methods Twenty-five pediatric patients (21 with tuberculosis, 2 with systemic juvenile idiopathic arthritis, 1 with inflammatory bowel disease, 1 with autoimmune hemolytic anemia) who received systemic steroids for 2–6 weeks and 25 age- and sexmatched controls were enrolled. BMC, BMD, and z scores of the whole body (WB), lumbar spine (LS), nondominant distal radius (DR), and total body less the head (TBLH) were determined by dual-energy x-ray absorptiometry at baseline, the end of steroid therapy or 6 weeks (whichever was earlier; first follow-up), and at the end of 3 months from baseline (second follow-up) in patients and at baseline in controls. The values were adjusted for confounding variables. Continuous and categorical variables were compared using Student t test and the chi-square test or Fisher exact test, respectively. Pairwise comparisons employed Bonferroni correction.Results Statistically significant decreases in BMC, BMD, and all z scores were observed. BMC declined by 5.37%, 2.08%, 1.82%, and 2.27%, and 11.42%, 3.75%, 3.34%, and 4.17% for WB, LS, DR, and TBLH, respectively, at the first and second follow-ups, respectively. Similarly, BMD declined by 2.01%, 2.31%, 2.18%, and 1.70% and 4.59%, 3.76%, 3.14%, and 3.50% for the WB, LS, DR, and TBLH, respectively, at the first and second follow-ups, respectively. A significant negative correlation was found among bone densitometric parameters, duration, and cumulative dose.Conclusion The use of systemic steroids for 2–6 weeks in pediatric patients decreased the BMD and BMC of trabecular and cortical bones, an effect that persisted after discontinuation.

Heated Tobacco Products Impair Cell Viability, Osteoblastic Differentiation, and Bone Fracture-Healing.

The negative impact of cigarette smoking on bone union has been well documented. However, the impact of heated tobacco product (HTP) use on bone fracture-healing remains unclear. The present study investigated the effect of HTPs on preosteoblast viability, osteoblastic differentiation, and fracture-healing and compared the effects with those of conventional combustible cigarettes. Cigarette smoke extracts (CSEs) were generated from combustible cigarettes (cCSE) and HTPs (hCSE). CSE concentrations were standardized by assessing optical density. Preosteoblast (MC3T3-E1) cells were incubated with normal medium, cCSE, or hCSE. The cell viability was assessed via MTT assay. After osteoblastic differentiation of CSE-exposed cells, alkaline phosphatase (ALP) activity was assessed. To assess the in vivo effects of CSEs, a femoral midshaft osteotomy was performed in a rat model; thereafter, saline solution, cCSE, or hCSE was injected intraperitoneally, and bone union was assessed on the basis of micro-computed tomography (μCT) and biomechanical analysis 4 weeks later. MC3T3-E1 cell viability was reduced in a time and concentration-dependent manner when treated with either cCSE or hCSE. ALP activity after osteoblastic differentiation of cCSE-treated cells was significantly lower than that of both untreated and hCSE-treated cells (mean and standard deviation, 452.4 ± 48.8 [untreated], 326.2 ± 26.2 [cCSE-treated], and 389.9 ± 26.6 [hCSE-treated] mol/L/min; p = 0.002). Moreover, the levels of osteoblastic differentiation in untreated and hCSE-treated cells differed significantly (p < 0.05). In vivo assessment of the femoral midshaft cortical region revealed that both cCSE and hCSE administration significantly decreased bone mineral content 4 weeks after surgery compared with levels observed in untreated animals (107.0 ± 11.9 [untreated], 94.5 ± 13.0 [cCSE-treated], and 89.0 ± 10.1 mg/cm3 [hCSE-treated]; p = 0.049). Additionally, cCSE and hCSE-exposed femora had significantly lower bone volumes than unexposed femora. Biomechanical analyses showed that both cCSE and hCSE administration significantly decreased femoral maximum load and elastic modulus (p = 0.015 and 0.019). HTP use impairs cell viability, osteoblastic differentiation, and bone fracture-healing at levels comparable with those associated with combustible cigarette use. HTP use negatively affects bone fracture-healing to a degree similar to that of combustible cigarettes. Orthopaedic surgeons should recommend HTP smoking cessation to improve bone union.

Female UK Army Service personnel are at greater risk of work-related morbidity on return to duty postpartum

IntroductionThe 2016 Interim Report on the Health Risks to Women in Ground Close Combat Roles highlighted an increased risk of skeletal injury and significant physiological changes, including increased ligament laxity...

Short-term stall housing of horses results in changes of markers of bone metabolism

In previous research, stall-housing growing horses resulted in decreased bone mineral content (BMC) of the third metacarpal (MCIII) compared to pasture-housing. To determine whether stall confinement negatively impacts bone, regardless of age, and whether the effects could be reversed upon return to pasture, 12 mature horses (5-15 years) and 12 yearlings were pair-matched by age and gender and randomly assigned to one of two treatment groups: pasture (PT) or stall (ST). Horses on PT remained there for the 84-d study, while horses on ST spent the first 28 d in stalls and the remaining 56 d on pasture. Radiographs and blood samples were taken on d 0 for baseline determinants. Radiographs and blood were taken every 7 d for radiographic photodensitometry estimates of BMC and analysis of osteocalcin (OC) and C-telopeptide (CTX-1)-markers of bone formation and degradation. There were no differences in BMC between treatments at the medial cortex of MCIII in mature horses. There were treatment (P=0.05) and day (P&lt;0.01) differences in BMC at the lateral cortex of MCIII. In yearling horses, the BMC of the medial cortex of MCIII had a day difference with the lowest overall average at d 21 and highest at d 70 (P=0.04). There were day by treatment differences (P&lt;0.05) for both OC and CTX-1 with the mature and yearling horses on ST having lower OC on d 14 than PT horses (P&lt;0.05) indicative of reduced bone formation. In mature and yearling ST horses, CTX-1 was greater on d 14 and 28 compared to horses on PT (P≤0.05) suggesting greater bone resorption. Results from serum markers of bone formation and deformation confirm that stalling negatively impacts bone formation in horses regardless of age.

PYY is a negative regulator of bone mass and strength.

ObjectiveBone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass.MethodsThe skeletal phenotype of Pyy knockout (KO) mice was investigated during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, back-scattered electron scanning electron microscopy (BSE-SEM), histomorphometry and biomechanical testing.ResultsBones from juvenile and Pyy KO mice were longer (P < 0.001), with decreased bone mineral content (P < 0.001). Whereas, bones from adult Pyy KO mice had increased bone mineral content (P < 0.05) with increased mineralisation of both cortical (P < 0.001) and trabecular (P < 0.001) compartments. Long bones from adult Pyy KO mice were stronger (maximum load P < 0.001), with increased stiffness (P < 0.01) and toughness (P < 0.05) compared to wild-type (WT) control mice despite increased cortical vascularity and porosity (P < 0.001). The increased bone mass and strength in Pyy KO mice resulted from increases in trabecular (P < 0.01) and cortical bone formation (P < 0.05).ConclusionsThese findings demonstrate that PYY acts as a negative regulator of osteoblastic bone formation, implicating increased PYY levels in the pathogenesis of bone loss during anorexia or following bariatric surgery.

Cross-sectional study of osteopenia of prematurity and associated risk factors

Background Survival of very low birth weight preterm neonates born at less than 32 weeks gestational age (GA) have continued to improve. In response to this increased survival, osteopenia of prematurity or metabolic bone disease of prematurity (MBDP) became a significant comorbidity. This latter is defined as decreased bone mineral content relative to the expected level of mineralization for a fetus or infant of comparable size or GA seen in conjunction with biochemical and/or radiological changes. Aim The aim of this work was to determine the prevalence of MBDP among neonates aged 6 weeks or more, born before the 32nd week GA and weighing less than 1500 g at birth. The predisposing and contributing factors for the development of the disease were also investigated. Patients and methods This cross-sectional descriptive study comprised 32 neonates aged 6 weeks or more, delivered before the 32nd week and weighing less than 1500 g at birth, among those admitted to the neonatal intensive care unit of Alexandria University Children’s Hospital. The study had been extended over a 6-month period. According to the radiological and biochemical screening tests for MBDP, namely serum Ca, P, and alkaline phosphatase, the babies were categorized as group 1: with biochemical evidence [serum phosphorous (P) 500 IU/l], group 2: with radiological evidence using Koo’s score, and group 3: with no radiological or biochemical evidence. In addition, the contributing and precipitating factors of this bone disease were revised. Results The prevalence of MBDP, based on the biochemical workup and radiological evidence, were 12.5 and 9.4%, respectively. Important risk factors included prematurity, prolonged duration of parental nutrition, delayed full enteral feeding, increased maternal parity, and extended use of theophylline and furosemide. Use of theophylline, low-serum P and high urinary calcium/creatinine (Ca/Cr) ratio were significant predictors of radiological evidence of the disease. Conclusion Routine screening of MBDP by biochemical and radiological means for all preterm infants less than 32 weeks GA is crucial to minimize the risk factors and bony complications and optimize mineral supplementation and enteral feeding.

Bone response around titanium alloy implants in osteoporosis

There has been a concerted effort among material scientists and clinicians worldwide to improve the performance of dental implants, with the aim of accelerating and maintaining their integration into hard and soft tissues and/or extend their range of application. The use of osseointegrated implants in the treatment of edentulous patients has become a common alternative to conventional prosthetic dentistry. The success of osseointegration depends in part on the state of the host bone and its healing capacity, and concerns have been raised about various conditions affecting its quality and quantity. Osteoporosis, which is a major health problem for the elderly population, is a reduction in the volume of bony tissue relative to the entire bone volume. The underlying clinical problem is a deficiency of bone mass. Because age and sex are reported to be important risk factors for osteoporosis, the rate of implant loss caused by the failure of osseointegration may also be expected to increase correspondingly. Thus, a large proportion of the target population for dental implants may be at high risk of implant failure. If so, the choice between conventional treatment and implant-supported prostheses in the prosthodontic treatment of older patients would need to be reassessed. For that reason, systems of dental care and plans for regenerative medicine need to be established based on an understanding of osteoporosis. Various experiments are being undertaken using osteoporotic models to obtain findings for that purpose. Effects such as delays in new bone formation in the maxilla and mandible and incomplete bone repair in the extraction socket in rat models with osteoporosis have been reported. In contrast, Mori et al. has reported that good osseointegration was obtained even in groups with decreased bone mineral content following ovariectomy. Shoji et al. reported that the effect of ovariectomy (OVX) on osteoprogenitors is either Bone response around titanium alloy implants in osteoporosis

Impact of Wheelchair Rugby on Body Composition of Subjects With Tetraplegia: A Pilot Study

ObjectiveTo investigate the longitudinal effects of wheelchair rugby (WR) training on body composition of subjects with tetraplegia. DesignSubjects were evaluated at baseline and after WR training. SettingFaculty of physical education settings. ParticipantsIndividuals with tetraplegia (N=13; age, 26.6±6.0y). InterventionsFour sessions per week of WR training composed by aerobic and anaerobic activities and technical and tactical aspects of WR. The average time of intervention was 8.1±2.5 months. Main Outcome MeasuresBody composition assessed by dual-energy x-ray absorptiometry. ResultsAfter training, fat mass was significantly reduced in the whole body (15,191±4603 vs 13,212±3318g, P=.016), trunk (7058±2639 vs 5693±1498g, P=.012), and legs (2847±817 vs 2534±742g, P=.003). Conversely, increased bone mineral content (183±35 vs 195±32g, P=.01) and fat-free mass (2991±549 vs 3332±602g, P=.016) in the arms and reduced bone mineral content in the trunk (553±82 vs 521±86g, P=.034) were observed after training. Furthermore, no significant correlation between the duration of training and changes in body composition was detected. ConclusionsRegular WR training increased lean mass and bone mineral content in the arms and decreased total body fat mass. Conversely, WR training was associated with decreased bone mineral content in the trunk. These results suggest that regular WR training improves body composition in subjects with tetraplegia.

Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet.

We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study.

Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7years of treatment. Data on longer follow-up are, however, scarce. Two hundred and thirty-adult GHD patients (mean age 47·1years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15years of rhGH replacement. In addition, clinical fracture incidence was assessed. Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000py. Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement.

Bone Mineral Density in Bulgarian Patients with Type 1 Diabetes Mellitus

Aim of the study: To examine the bone mineral density (BMD) in Bulgarian patients with type 1 diabetes mellitus (DM) in comparison to age- sex- and ethnically matched healthy controls and its correlation with bone turnover markers: oteocalcin as a marker of bone formation and deoxypyridinoline cross-laps as bone resorption marker. Materials and methods: 162 patients with type 1 DM (97 females and 65 males) age 29.17 yrs. (20-40) and 200 (100 women and 100 men) age- and sex matched healthy controls were analyzed for BMD and Z-score of lumbar spine and femoral neck by dual X-ray absorptiometry (DXA) using Lunar DPX-A. Plasma levels of osteocalcin and urine levels of deoxypyridinoline cross-laps were determined. Results: BMD in type 1 DM showed statistically significant lower levels for lumbar spine L1-L4- men (1.2114 g/ cm2 ± 0,1587 DM vs. 1.3346 g/ cm2 ± 0,1635 controls, P<0.05) and L1-L4 women (1.1035 g/cm2 ± 0.1269 DM vs 1.1978 g/ cm2 ± 0,1269 controls, P<0.05) and femoral neck - men (0.9138 g/cm2 ± 2134 DM vs 0.9868 g/ cm2 ± 0.1534 controls, P<0.05) and women (0.8656 g/cm2 ± 0.1223 DM vs 0.9236 g/ cm2 ± 0.145 controls, P<0.05) in both sexes in comparison with that in control group. We found no statistically significant difference for osteocalcin levels as a marker of bone formation in both groups (P=0.062), while deohypyridinoline (DPD) levels as a marker of bone resorption were significantly higher (P<0.01) in diabetic patients in comparison with age and sex matched controls. Osteocalcin showed significant negative correlation with BMD at lumbar spine (r=-0.418; P=0.004) and nonsignificant negative correlation with that at femoral neck (r=-0.271; P=0.078) in diabetic patients. DPD showed nonsignificant correlations with BMD at lumbar spine (r=-0.024; P=0.846) and at femoral neck (r=0.143; P=0.259) in diabetic patients. Conclusions: BMD measured at lumbar spine and femoral neck was significantly lower in patients with type 1 DM than in age-and sex matched controls. Levels of the bone turnover markers indicate increased bone resorption as a reason for the decreased bone mineral content in diabetic patients. Prospective studies are needed to determine whether metabolic control of diabetes has any influence upon the observed bone changes and whether keeping good metabolic control can minimize the reduction of the bone mineral content like it happens with the diabetic microangioapthy. If we consider the reduction of the BMD to be a specific complication of type 1 diabetes mellitus than we should take appropriate measures to cope with this problem like stressing upon the importance of appropriate diet adequate physical activity especially at the time peak bone mass is being accumulated.

Serum Sclerostin Levels Are Decreased in Adult Patients With Different Types of Osteogenesis Imperfecta

There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown. We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI. This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls. Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss.

A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

Rat tail suspension is an accepted method to create experimental osteopenia. However, suspension periods longer than 3 wk may cause tail skin sloughing or rat slippage. The hypothesis was that a traction system with skeletal anchorage through one tail vertebra would prolong the suspension time without significant complications. There were 80 young adult female Wistar rats that were submitted to one of the following interventions: skeletal tail suspension (N = 20), skin tail suspension (N = 20), no intervention (N = 20), and a baseline control (N = 20). All animals were followed up either for 3 (N = 10) or 6 (N = 10) wk. Animals were assessed for clinical signs of stress and tolerance to suspension. The femur evaluation was in terms of mineral density content, mechanical resistance, and histomorphometry. All animals reached the 3-wk end point. However, for the 6-wk period, seven animals suspended by the skin traction method were discarded (70%) because of signs of stress and skin sloughing. In contrast, there was one loss in the skeletal suspension group (10%). All suspended animals developed similar osteopenia at 3 wk characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass. At 6 wk, all suspended animals had similar osteopenic parameters, but they were not statistically different from those of the rats in the 3-wk groups. Therefore, suspension longer than 3 wk did not increase the bone deterioration in the femur.

Vitamin-D regulation of bone mineralization and remodelling during growth

Vitamin D status relates to two bone diseases, osteomalacia and osteoporosis which arise from distinct pathophysiogical pathways. They can occur in children as well as adults. Osteomalacia or rickets arises from a delay in mineralization and can be caused by severe vitamin D deficiency where the key to curing osteomalacia is the endocrine action of circulating 1,25-dihydroxyvitamin D to normalize the active intestinal transport of calcium and phosphate. Osteoporosis or sub-optimal bone mineral accretion during growth is a risk factor for fracture in children. Current evidence suggests serum 25-hydroxyvitamin D levels between 20 and 80 nmol/L are associated with decreased bone mineral content as a result, at least partly, of reduced vitamin D metabolism and activity within bone cells. The local synthesis of 1,25-dihydroxyvitamin D within bone is necessary to modulate bone resorption and promote bone formation. Thus an adequate vitamin D status is necessary for vitamin D activity within bone to establish a healthy skeleton.

Effets de la restriction alimentaire appliquée à des rates adultes sur la croissance osseuse et la structure histologique de la thyroïde chez leurs jeunes

Study purposeOur objective was the study of the development and the maturation of pups whose mothers were subjected to intermittent fasting. Materials and methodsEight pregnant female Wistar rats were distributed into two groups of four adult females. The rats of the first group were subjected to intermittent fasting beginning on the 14th day of gestation and continued 21 days after parturition. The rats of the second group were normally fed. The young of both groups of rats were sacrificed at the age of 21 days. ResultsThe pups of the female rats submitted to food restriction showed a reduction of the body weight (–35%), of the thyroid iodine content (P<0.001) and of segment thyroxin (P<0.05). The histological study revealed that these pups presented colloid depletion of this follicular thyroid, non-anastomosing trabeculae, cortical bone thinning, decreased bone mineral content, absence of osteoid formation and decreased number of osteoclasts. ConclusionDietary restriction imposed on adult rats, from gestation, led to the installation in their pups of a state of malnutrition and a description of thyroid histology. This thyroid abnormality is associated with hypothyroidism that led, at least in part, to the collapse of the ability to regulate bone remodeling.