Bone Mass Gain Research Articles

Bone Mass Outcomes in Patients With Osteoporosis Treated With Risedronate After Alendronate Failure: a 12-Month Follow-Up Study

Oral bisphosphonates are the drugs most frequently used for the treatment of osteoporosis. Clinicians usually switch between these drugs in clinical practice based on differences in efficacy. We aim to investigate the reasons associated with switching between oral bisphosphonates and to evaluate bone mass response and the incidence of fractures 12 mo after the exchange in a cohort of patients with osteoporosis seen at a tertiary hospital. Patients with osteoporosis who switched between oral bisphosphonates between January 2007 and December 2014 were included. Bone mass measured by dual-energy X-ray absorptiometry and the incidence of fracture were evaluated. A total of 112 patients (73.1 yr old on average, 95.5% women, 98% postmenopausal) were included. All patients were taking alendronate at the time of the switch to risedronate. In 91 patients (81.3%), the following reasons for the exchange of medication were identified: bone loss (59.8%), adverse events (11.6%), and recent fragility fracture (10.7%). One year after the switch, bone densitometry revealed bone loss in 51 patients (45.5%), bone mass maintenance in 34 (30.4%), and bone mass gain in 27 (24.1%). No new vertebral fracture was detected and no nonvertebral fracture was reported in 12 mo of follow-up. Bone mass outcomes (gain, loss, or maintenance) were not associated with the reason for switching between oral bisphosphonates. Similarly, none of the parameters evaluated could predict good densitometric response (gain or maintenance) in this scenario. Our findings suggest that the use of risedronate should not be recommended in the scenario of treatment failure or adverse events following the use of alendronate.

Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults.

WNT proteins comprise a 19-member glycoprotein family that act in several developmental and regenerative processes. In bone, WNT proteins regulate osteoblast differentiation and maintain bone health by activating the canonical WNT/β-catenin pathway. We reported a heterozygous missense mutation c.652T>G (p.C218G) in WNT1 exon 4 as the cause for severe early-onset, autosomal dominant osteoporosis. The initial study concerned a large Finnish family with 10 affected adults. Here we report clinical findings of the WNT1 osteoporosis in 8 children and young adults (median age 14 years; range 10 to 30 years) in two families, all with the p.C218G mutation in WNT1. Clinical assessments showed no apparent dysmorphia or features similar to typical osteogenesis imperfecta (OI). Biochemistry revealed no changes in parameters of calcium metabolism and bone turnover markers. Fracture frequencies varied, but all subjects had sustained at least one fracture and 4 had a pathological fracture history. Plain radiographs showed osteopenic appearance, loss in vertebral height, and thin diaphyses of the long bones. Bone densitometry showed the BMD to be below normal median in all subjects and the bone mass deficit seemed to be more severe in older participants. Bone histomorphometry revealed a low turnover osteoporosis in 2 subjects at ages 14 and 16 years. These findings are congruent with earlier findings in adult patients and indicate that WNT1 osteoporosis causes significant skeletal changes already in early childhood and impairs bone mass gain during pubertal years. Genetic testing of children or close relatives of affected individuals is recommended for appropriate preventive measures. © 2016 American Society for Bone and Mineral Research.

Use of a Titanium Mesh "Shelter" Combined with the Soft Tissue Matrix Expansion (Tent Pole) Grafting in the Reconstruction of a Severely Resorbed Edentulous Mandible. Technical Note.

Patients wearing complete dentures for a long time usually exhibit lack of bone and keratinized mucosa in the bearing area due to bone resorption. The patients suffering from this phenomenon usually have unstable and non-retentive complete denture, which result in constant trauma to the mucosa, pain, functional limitations and worsening of facial esthetics. An innovative technique has been described in which a novel surgical approach using osseointegrated dental implants as "tent poles" was applied concomitant with particulate autogenous bone graft. The authors claim that the control and maintenance of the surgically expanded soft tissue volume should prevent graft resorption in the long term. Nevertheless, resorption of the bone graft is usually more significant where the bone mass is poorer, in the mandibular body. This paper describes a case of severely resorbed edentulous mandible in which the "tent pole" technique was applied with some modifications. Use of the titanium mesh "shelters" and two additional implants was effective in "protecting" the bone graft in the posterior portion of the mandibular body increasing bone mass volume in this area. Furthermore, we believe that this kind of graft "protection" on the whole residual alveolar ridge can increase the width of bone mass gain optimizing the "tent pole" technique.

Anabolic Steroids Improve Bone Mineral Density and Quality of Life in Patients with Osteoporotic Fractures Around the Hip

AIM: Osteoporotic fractures cause considerable morbidity and disability in both women and men. The current prospective study was designed to identify the effect of anabolic steroids in patients with osteoporotic fractures around the hip. METHODS: A total of 248 patients with unilateral osteoporotic hip fractures (t≤-2.5, as measured by a DEXA of the contra-lateral hip) were included in the study and divided into two groups randomly. Group 1 comprising of 132 patients, was given Nandrolone 50 milligrams once a week for 5 weeks, along with 500 mg of elemental calcium and 0.25 micrograms of calcitriol once daily for 3 months, starting from the next day of surgery. Group 2 comprising of 116 patients was given only 500 mg of elemental calcium and 0.25 micrograms of calcitriol once daily for 3 months from the first post operative day. In group 1 eight patients expired and 24 were lost to follow up, leaving a total of 100 patients at the final follow up of 1 year; while in group 2 ten expired and 20 were lost to follow up leaving a total of 86 at final follow up. The patients were evaluated at 3, 6 and 12 months for BMD, Katz index for activities of daily living and functional improvement. RESULTS: In Group 1 it was observed that the mean t-score improved from -2.9160.573 at presentation to -2.112±0.599 at 12 months. The mean Harris Hip Score was 85.44±10.56 and the Katz index of independence in activities of daily living showed marked improvement. The patients of group 2 showed less marked improvement in their mean t-scores as well as the mean Harris hip score and the Katz index. CONCLUSION: The current study suggests that the use of low dose anabolic steroids results in a significant gain in bone mass and improvement in quality of life in geriatric population, but comparative studies with a larger sample size and longer follow up are required to further support this observation.

Bone tissue: rebuilding and inflammation

In this review the author summarizes the knowledge related to structural elements of bone tissue. The process of bone reorganisation and knowledge about the special feature of bone metabolism in human are also discussed. It is noted that due to the reorganisation, there is a complete renewal of bone tissue in every 10 years, and this renewal lasts throughout the life. However, there are life periods when osteoclast activity is low, e.g. in childhood and the second decade of life when the gain of bone mass may be as much as 40% of the final bone mass. Overactivity of osteoclasts occurs at age 60 years in men and somewhat earlier in women. Reorganization of bone tissue is an elementary requirement for the physiological functions (locomotion, hemopoiesis, immune functions). The RANK-RANKL-osteoprotegerin axis plays an important role in the regulation of bone metabolism. Bone mass is dependent on osteocytes; osteoblasts are building up while osteoclasts are reabsorbing bone tissue. In this process transcription factors, hormone-like substances and a large number of cytokines are involved. In addition, the inflammatory process within the bone tissue as well as the defending, reparative inflammation and specific immune response are of great importance in bone reorganisation. This is particularly valid for α2-macroglobulin and transforming growth factor, although the exact role in bone reorganization has not been fully explored. It can be concluded that the elements, which participate in bone reorganization and in defending inflammatory and specific immunological processes, are essentially identical. Therefore, the existence of an osteo-immunological complex system has emerged.

Suppression of NF-κB activation by gentian violet promotes osteoblastogenesis and suppresses osteoclastogenesis.

Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures are associated with significant morbidity and in the case of hip fractures, high mortality. Gentian violet (GV), a cationic triphenylmethane dye, has long been used as an antifungal and antibacterial agent and is presently under investigation as a potential chemotherapeutic and antiangiogenic agent. However, effects on bone cells have not been previously reported and the mechanisms of action of GV, are poorly understood. In this study we show that GV suppresses receptor activator of NF-κB ligand (RANKL)-induced differentiation of RAW264.7 osteoclast precursors into mature osteoclasts, but paradoxically stimulates the differentiation of MC3T3 cells into mineralizing osteoblasts. These actions stem from the capacity of GV to suppress activation of the nuclear factor kappa B (NF-κB) signal transduction pathway that is required for osteoclastogenesis, but inhibitory to osteoblast differentiation and activity. Our data reveal that GV is an inhibitor of NF-κB activation and may hold promise for modulation of bone turnover to promote a balance between bone formation and bone resorption, favorable to gain of bone mass.

MP70-07 THE EFFECT OF ADDITIONAL PATHOLOGIC FEATURES ON CANCER SPECIFIC SURVIVAL FOLLOWING RADICAL PROSTATECTOMY IN MEN WITH SEMINAL VESICLE INVASION

CONCLUSIONS: PCa patients under ADT, and with confirmed severe osteopenia or osteoporosis, showed a significant increase in bone mass when treated either with denosumab or alendronate for one year. While denosumab increased significantly bone mass in all three DXA standard sites, alendronate did not at total hip. Any significant bone mass gain was observed in men previously treated with alendronate who switched to denosumab treatment.

Evaluation of chronic low back pain in osteoporotic patients in treatment with teriparatide

OBJECTIVE: The objective was to assess the improvement of chronic low back pain in osteoporotic patients treated with teriparatide (TPTD). METHODS: This was an observational study with a convenience sample of 21 patients with osteoporosis using TPTD, 20 mcg/day, between 2006 and 2010, with chronic low back pain (more than three months). Dorsolumbar radiographs and bone densitometry (DXA) were performed before and after treatment. For pain measurement the VAS pain scale was used. Data were entered in Excel and processed in STATA/SE 8.0 with Chi2 square or Fisher (p < 0.05). RESULTS: twenty-one patients aged 40-90 (mean 70 years), eight (40%) had senile osteoporosis and thirteen (60%) had osteoporosis secondary to medications. Seventeen (80%) had previous dorsolumbar fractures. Ten (47.5%) used TPTD for 24 months, six (27.5 %) used the medication for 18 months, four (20%) for 12 months and one (5%) for six months. Eight patients (40%) received previous anti-reabsortive therapy. Thirteen patients (60%) exhibited bone mass gain between 0% and 9% while eight (40%), between 10% and 15%. The final average VAS was 2.6 representing an improvement of 4.7 (p< 0.05). CONCLUSION: There was a significant reduction in the severity of low back pain with the use of TPTD (initial mean VAS: 7.3, final VAS: 2.6, improvement: 4.7).

Risedronate improves bone architecture and strength faster than alendronate in ovariectomized rats on a low-calcium diet

Clinical evidence suggests that, compared with alendronate, risedronate reduces fracture risk faster and more potently, with less bone mass gain. We tested the hypothesis that risedronate improves bone quality faster than alendronate using calcium-deficient, ovariectomized (OVX) rats. Female Sprague-Dawley rats at 24 weeks of age were divided into sham-operated and OVX groups and fed a low-calcium (0.05%) diet under paired feeding. After 12 weeks, OVX rats were divided into five groups and treated with vehicle, risedronate (3.5 and 17.5 μg/kg/week, s.c.) or alendronate (7 and 35 μg/kg/week, s.c.). Rats were killed 6-8 weeks later and the bone architecture and strength of the left femur were evaluated by micro-computed tomography and a three-point bending test. Trabecular bone mineral density (BMD), number and thickness were significantly lower in OVX rats than in the sham-operated group. Cortical BMD, bone area (Ct.Ar), and thickness (Ct.Th) were similarly decreased. Risedronate significantly improved Ct.Ar (+8%) and Ct.Th (+9%) at 6 weeks, while alendronate only caused a significant improvement in Ct.Ar (+8% at 6 weeks) and only at the higher dose. At 8 weeks, both risedronate and alendronate significantly increased trabecular BMD compared with the vehicle. Bone strength parameters showed a significant correlation between Ct.Ar and Ct.Th. Risedronate significantly improved maximum load at 6 weeks, while alendronate failed to produce any significant changes. Our results suggest that risedronate is superior to alendronate at improving cortical bone architecture and strength, and that enhanced bone quality partly accounts for risedronate's efficacy.

Fructus ligustri lucidi Ethanol Extract Improves Bone Mineral Density and Properties Through Modulating Calcium Absorption-Related Gene Expression in Kidney and Duodenum of Growing Rats

Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague-Dawley rats were randomized into four groups and orally administrated for 4 months an AIN-93G formula-based diet supplementing with different doses of FLL ethanol extract (0.40, 0.65, and 0.90 %) or vehicle control, respectively. Then calcium balance, serum level of Ca, P, 25(OH)2D3, 1,25(OH)2D3, osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX-I), and parathyroid hormone, bone microarchitecture, and calcium absorption-related genes expression in duodenum and kidney were analyzed. The results demonstrated that FLL ethanol extract increased BMD of growing rats and improved their bone microarchitecture and mechanical properties. FLL ethanol extract altered bone turnover, as evidenced by increasing a bone formation maker, OCN, and decreasing a bone resorption maker, CTX-I. Intriguingly, both Ca absorption and Ca retention rate were elevated by FLL ethanol extract treatment, possibly through the mechanisms of up-regulating the transcriptions of calcitropic genes in kidney (1α-hydroxylase) and duodenum (vitamin D receptor, calcium transporter calbindin-D9k, and transient receptor potential vanilloid 6). In conclusion, FLL ethanol extract increased bone mass gain and improved bone properties via modulating bone turnover and up-regulating calcium absorption-related gene expression in kidney and duodenum, which could then activate 1,25(OH)2D3-dependent calcium transport in male growing rats.

Femoral neck bone adaptation to weight-bearing physical activity by computational analysis

Individual differences in bone mass distribution at the proximal femur may be determined by daily weight-bearing physical activity (PA) since bone self-adapts according to the mechanical loads that is submitted. The aim of this study was to analyse computationally the effect of different weight-bearing PA types in the adaptation of the femoral neck (FN) by analysing regional differences in bone mineral density (BMD) at the integral FN and its superior, inferior, anterior and posterior subregions. To achieve this, it was adopted a 3-D femoral finite element (FE) model coupled with a suitable bone remodeling model. Different PA types were determined based both on ordinary lifestyle and mechanically more demanding PA as low magnitude impacts (L–I), moderate-magnitude impacts from odd directions (O–I) and high-magnitude vertical impacts (H–I). It was observed that as time spent in weight-bearing PA increases, BMD augment around the integral FN, but with different bone mass gain rates between subregions depending on the magnitude and directions of the hip contact forces; H–I was the type of weight-bearing PA which structurally most favor the gain of bone mass superiorly at the FN while both the H–I and the O–I types of PA promoted the largest bone mass gain rates at the anterior and posterior subregions of the FN. Because these types of weight-bearing PA were associated with a more uniform bone mass spatial distribution at the FN, they should provide a potential basis for targeted PA-based intervention programs for improving hip strength.

Specific Bone Mass Acquisition in Elite Female Athletes

Cross-sectional studies have demonstrated that physical activity can improve bone mass acquisition. However, this design is not adequate to describe the specific kinetics of bone mass gain during pubertal development. To compare the kinetics of bone mass acquisition in female adolescent athletes of sports that impose different mechanical loads and untrained controls throughout puberty. A total of 72 girls with ages ranging from 10.8 to 18.0 years were recruited: 24 rhythmic gymnasts (RG, impact activity group), 24 swimmers (SW, no-impact activity), and 24 age-matched controls (CON). Areal bone mineral density (aBMD) was determined using dual-energy x-ray absorptiometry and bone turnover markers were analyzed. All the investigations were performed at baseline and after 1 year. At baseline and after 1 year of follow-up, RG presented significantly greater aBMD adjusted for age, fat-free soft tissue, and fat mass compared with CON and SW, only at the femoral region. When aBMD variation throughout the pubertal period was modeled for each group from individual values, the aBMD at the femoral region was significantly higher in RG compared with the other 2 groups from 12.5 to 14 years, and this difference lasted up to 18 years. Moreover, the mean annual aBMD gain tended to be higher in RG compared with SW and CON only at the femoral region and this gain lasted longer in RG. Bone remodeling markers decreased similarly with age in the 3 groups. This study, which was based on linear mixed models for longitudinal data, demonstrated that the osteogenic effect of gymnastics is characterized by greater bone mass gain localized at mechanically loaded bone (ie, the proximal femur) principally around the menarcheal period. Moreover, the bone mass gain lasts longer in gymnasts, which may be explained by the delay in sexual maturation.

Positive regulation of osteogenesis by bile acid through FXR

Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR(-/-) ) in vivo resulted in a significant reduction in bone mineral density by 4.3% to 6.6% in mice 8 to 20 weeks of age compared with FXR(+/+) mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, tartrate-resistant acid phosphatase (TRACP) staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR(-/-) mice compared with FXR(+/+) mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR(-/-) mice compared with FXR(+/+) mice in concert with a significant reduction in type I collagen a1(Col1a1), ALP, and runt-related transcription factor 2 (Runx2) gene expressions. Cultures of bone marrow-derived macrophages from FXR(-/-) mice exhibited an increased number of osteoclast formations and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). In female FXR(-/-) mice, although bone mineral density (BMD) was not significantly different from that in FXR(+/+) mice, bone loss was accelerated after an ovariectomy compared with FXR(+/+) mice. In vitro, activation of FXR by bile acids (chenodeoxycholic acid [CDCA] or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced extracellular signal-regulated kinase (ERK) and β-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol (FOH 1%) diet marginally prevented ovariectomy (OVX)-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways; ie, bone formation and resorption.

Will PPAR-γ agonist therapy still have a role in diabetes management in 2013?

SUMMARY Thiazolidinediones have been used for treatment of Type 2 diabetes since the late 1990s. They act as ligands for PPAR-γ, activating hundreds of genes in many tissues. Their actions result in favorable (insulin-sensitizing) and unfavorable (fluid retention, weight gain and decrease in bone mass) effects. This article describes the dilemma encountered by clinicians contemplating the use of these agents to improve diabetes control in the current environment, which is currently focused on ‘protecting’ the patient from the putative harm ascribed to rosiglitazone (ischemic myocardial events) and pioglitazone (bladder cancer) rather than the benefits of these therapies.

Biomechanical properties of the mandible, as assessed by bending test, in rats fed a low-quality protein

ObjectiveThe present study describes the effects of feeding growing rats with diets containing increasing concentrations of wheat gluten (a low quality protein, G) on both the morphometrical and the biomechanical properties of the mandible. DesignFemale rats were fed one of six diets containing different concentrations (5–30%) of G between the 30th and 90th days of life. Control rats were fed a diet containing 20% casein (C), which allows a normal growth and development of the bone. Mandibular growth was estimated directly on excised and cleaned bones by taking measurements between anatomical points. Mechanical properties of the right hemimandibles were determined by using a three-point bending mechanical test to obtain a load/deformation curve and estimate the structural properties of the bone. Bone material properties were calculated from structural and geometric properties. The left hemimandibles were ashed and the ash weight obtained. Calcium content was determined by atomic energy absorption. Results were summarised as means±SEM. Comparisons between parameters were performed by ANOVA and post-test. ResultsNone of the G-fed groups could achieve a normal growth performance as compared to the C-fed control group. Like body size, age-related increments in mandibular weight, length, height and area (index of mandibular size) were negatively affected by the G diets, as was the posterior part of the bone (posterior to molar III). The cross-sectional geometry of the mandible (cross-sectional area and rectangular moment of inertia) as well as its structural properties (yielding load, fracture load, and stiffness) were also severely affected by the G diets. However, material properties (Young's modulus and maximum elastic stress) and calcium concentration in ashes and the degree of mineralisation were unaffected. ConclusionsThe differences in strength and stiffness between treated and control rats seemed to be the result of an induced loss of gain in bone growth and mass, in the absence of changes in the quality of the bone mineralised material.

Osteoporosis and trace elements – An overview

More than 200 million people are affected by osteoporosis worldwide, as estimated by 2 million annual hip fractures and other debilitating bone fractures (vertebrae compression and Colles’ fractures). Osteoporosis is a multi-factorial disease with potential contributions from genetic, endocrine functional, exercise related and nutritional factors. Of particular considerations are calcium (Ca) status, vitamin D, fluoride, magnesium and other trace elements. Several trace elements such as zinc and copper are essential for normal development of the skeleton in humans and animals. Fluoride accumulates in new bone and results in a net gain in bone mass, but may be associated with a tissue of poor quality. Aluminum induces impairment of bone formation. Gallium and cadmium suppresses bone turnover. However, exact involvements of the trace elements in osteoporosis have not yet been fully clarified. Numerous investigators have evaluated the role of medications and supplementations with minerals and trace substances to reverse the progression of this disease. Although bisphosphonates are still the drugs of choice, low-dosed fluoride and strontium salts have shown promise for the future.

Human Adipose Tissue-Derived Stromal Cell Therapy Prevents Bone Loss in Ovariectomized Nude Mouse

Osteoporosis is a skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of cell therapy of human adipose tissue-derived stromal cell (ADSC) on ovariectomy-induced bone loss in T cell deficient nude mice. Twelve-week-old female nude mice underwent ovariectomy and were treated with ADSC, estrogen, or phosphate buffered saline (PBS). Whole body BMD revealed that treatment of ADSC was more protective against ovariectomy-induced attenuation in bone mass gain compared with PBS control after cell therapy (8.4±1.1 vs. 2.4%±1.4%, p<0.05 at 4 weeks, 13.7±1.3 vs. 7.7%±1.8%, p<0.05 at 8 weeks) and this effect was comparable to that of estrogen. μCT analysis revealed that the effect of ADSCs was specific to trabecular bone. Serum osteocalcin levels were increased 4 weeks after ovariectomy and treatment with ADSCs (76.4±11.6 ng/mL) increased osteocalcin to a greater extent when compared with estrogen (63.1±6.7 ng/mL, p<0.05) or PBS treatment (58.0±9.2 ng/mL, p<0.05). Flow cytometry analysis for PKH26-labeled ADSCs and quantitative real-time PCR analysis for human β-globin from bone revealed that transplanted ADSCs were trafficking in bone 48 h after injection and subsequently disappeared. There was no evidence of long-term engraftment of infused ADSCs in bone. In vitro, treatment with ADSC-conditioned medium enhanced osteogenic differentiation in stromal cells and preosteoblasts. These results suggest that cell therapy of ADSCs protects against ovariectomy-induced bone loss in nude mice in a paracrine manner.

Growth-dependent effects of dietary protein concentration and quality on the biomechanical properties of the diaphyseal rat femur

ObjectivesThis study compares the effects of feeding growing rats with increasing concentra-tions of casein (C) and wheat gluten (G), proteins that show different biological qualities, on the morphometrical and biomechanical properties of the femoral diaphysis. Materials and methodsFemale rats were fed with one of ten diets containing different con-centrations (5–30%) of C and G between the 30th and 90th days of life (Control = C-20%). Biomechanical structural properties of the right femur middiaphysis were estimated using a 3-point bending mechanical test with calculation of some indicators of bone material properties. ResultsBody weight and length were affected by treatments, values being highest in rats fed the C-20% diet. G diets affected negatively both parameters. Changes in cross-sectional geome-try (mid-diaphyseal cross-sectional and cortical areas, femoral volume, and rectangular moment of inertia) were positively related to the C content of the diet, while they were severely and negatively affected by G diets. Similar behaviors were observed in the bone structural properties (fracture load, yielding load, diaphyseal stiffness and elastic energy absorption). When values of strength and stiffness were normalized for body weight, the differences disappeared. The bone material quality indicators (elastic modulus, yielding stress, elastic energy absorption/volume) did not differ significantly among all studied groups. Femoral calcium concentration in ashes was not significantly different among groups. ConclusionThe clear differences in strength and stiffness of bone beams induced by dietary protein concentration and quality seemed to be the result of an induced subnormal gain in bone structural properties as a consequence of a correlative subnormal gain in bone growth and mass, yet not in bone material properties.

Bone disease in pediatric idiopathic hypercalciuria

Idiopathic hypercalciuria (IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density (BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs (gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins (i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.

Therapeutische und prophylaktische Effekte von Sport und Training bei Osteoporose und Fraktur Risiko

Osteoporosis and low bone strength in older people may be due to low bone mass accrual or elevated age-related loss of bone mass. The mechanisms underlying loss of bone mass have long been subjected to research. However, research has only started in the last decade to focus on strategies to increase bone mass:the current opinion is that childhood and adolescence are critical periods for building up bone mineral density. It is also known that life style factors, such as physical activity may influence the accrual of bone mineral density Mechanical loading has been shown to be one of the best stimuli to enhance not only bone mass but also structural skeletal adaptations. both independently contributing to bone strength. Exercise prescription also includes a window of opportunity to improve bone strength in the late pre- and early pen-pubertal period. There is some evidence supporting the notion that gains inbone mass obtained by mechanical loading during growth are maintained at older age despite reduction of physical activity in adulthood. The notion that former male athletes have a lower fracture risk compared to non-athlets of the same age suggests that physical activity during growth and adolescence should be recommended as a feasible strategy to reduce the future incidence of fragility fractures. (Less)