Loss Of Bone Strength Research Articles

A clinical study on the 6-year outcomes of immediately loaded three implants for completely edentulous mandibles: "the all-on-3 concept".

The objective of the current study was to demonstrate the 6-year clinical and radiological treatment outcomes of the technique performed by immediately loading of three implants (single straight in the mid-line and two tilted distal implants) for the management of total edentulous mandibles and introduce a simple decision matrix for selection of the most appropriate protocol in cases with insufficient length of the interforaminal area. Re-assessments were performed over a total observation period of 6years after surgery via measurement of bone resorption around implants, bleeding on probing, plaque accumulation, periodontal probing depth, bite force measurements and oral health impact profile. A total of 29 patients (45% women and 55% men) with a mean age of 65 ± 6years enrolled in the study. 14 patients received an acryl-based bridge as definitive prosthetic restoration and 15 patients received a ceramic-based restoration. Both during the immediate loading phase and during the 6-year follow-up, there was no implantation loss. Regardless of the implant position, all implants showed continuous bone loss over the observation time. The bone loss around dental implants during observation period was only maximum 1.0 ± 1mm and it remained well within the limits for 'success' according to the 2007 Pisa consensus (< 2mm). The plaque index showed no significant fluctuations between the implant positions and the individual examination times. The approach described herein might help the surgeon by avoiding unnecessary loss of bone strength, selecting implant sites, and establishing the biomechanical advantage of increased A-P spread for immediate function.

Anti-interleukin-6 receptor antibody prevents loss of bone structure and bone strength in collagen-induced arthritis mice

Objective: Rheumatoid arthritis (RA) is a disease that typically induces secondary osteoporosis, which increases the risk of bone fractures. Anti-interleukin-6 (IL-6) receptor antibody is used to treat RA; however, its effect on bone strength is not clear. Therefore, we investigated the influence of MR16-1, an anti-mouse IL-6 receptor antibody, on bone structure and femoral strength in a collagen-induced arthritis (CIA) mouse model.Method: DBA/1J mice were immunized by intradermal injection of bovine type II collagen. MR16-1 was administered intraperitoneally at the same time as immunization. Thirty-five days after the first immunization, bone structure and bone strength were measured by micro-computed tomography and the three-point bending test.Results: In the CIA group, most bone mineral density and bone structure parameters in the foot, femur, and lumbar spine were significantly lower than in the normal group. Moreover, the maximum load of the femoral shaft in the CIA group was significantly lower than in the normal group. MR16-1 treatment significantly prevented the CIA-induced deterioration of bone structure and loss of bone strength.Conclusion: These results suggest that CIA systemically induces a deterioration of bone structure and loss of bone strength, and that IL-6 signalling plays an important role in these processes.

PTH (1–34) and growth hormone in prevention of disuse osteopenia and sarcopenia in rats

Osteopenia and sarcopenia develops rapidly during disuse. The study investigated whether intermittent parathyroid hormone (1-34) (PTH) and growth hormone (GH) administered alone or in combination could prevent or mitigate disuse osteopenia and sarcopenia in rats. Disuse was achieved by injecting 4IU botulinum toxin A (BTX) into the right hindlimb musculature of 12-14-week-old female Wistar rats. Seventy-two rats were divided into six groups: 1. Baseline; 2. Ctrl; 3. BTX; 4. BTX+GH; 5. BTX+PTH; 6. BTX+PTH+GH. PTH (1-34) (60μg/kg/day) and GH (5mg/kg/day). The animals were sacrificed after 6weeks of treatment. Sarcopenia was established by histomorphometry, while the skeletal properties were determined using DXA, μCT, mechanical testing, and dynamic bone histomorphometry. Disuse resulted in lower muscle mass (-63%, p<0.05), trabecular BV/TV (-28%, p<0.05), Tb.Th (-11%, p<0.05), lower diaphyseal cortical thickness (-10%, p<0.001), and lower bone strength at the distal femoral metaphysis (-27%, p<0.001) compared to Ctrl animals. PTH fully counteracted the immobilization-induced lower BV/TV, Tb.Th, and distal femoral metaphyseal strength. GH increased muscle mass (+17%, p<0.05) compared to BTX, but did not prevent the immobilization-induced loss of bone strength, BV/TV, and cortical trabecular thickness. Combination of PTH and GH increased distal femoral metaphyseal bone strength (+45%, p<0.001), BV/TV (+50%, p<0.05), Tb.Th (+40%, p<0.05), and whole femoral aBMD (+15%, p<0.001) compared to BTX and muscle mass (+21%, p<0.05) compared to BTX+PTH. In conclusion, PTH and GH in combination is more efficient at preventing the disuse-related deterioration of bone strength, density, and micro-architecture than either PTH or GH given as monotherapy. Furthermore, GH, either alone or in combination with PTH, attenuated disuse-induced loss of muscle mass. The combination of PTH and GH resulted in a more effective treatment than PTH and GH as monotherapy.

Bone-Muscle Crosstalk: Unraveling New Therapeutic Targets for Osteoporosis.

Osteoporosis is a condition featured by bone mass loss and bone tissue microarchitectural alterations due to impaired tissue homeostasis favoring excessive bone resorption versus deposition. The trigger of such an impairment and the downstream molecular pathways involved are yet to be clarified. The natural course of osteoporosis is particularly worrisome because, through a "silent" progression, it enhances bone fragility, increases the risk of fractures and is associated with increased risk of disability and mortality. To date, the assessment of bone mineral density by dual-energy X-ray absorptiometry, represents the non-invasive gold standard for the evaluation of bone mineralization and the diagnosis of osteoporosis. Although long known as a condition merely related to the hormonal-driven loss of bone homeostasis, emerging evidence supports the need of reframing osteoporosis in the context of structural and functional changes of the musculoskeletal system as a whole. Several age-related alterations of bone microenvironment and an altered bone-muscle crosstalk have been suggested to be relevant contributors to loss of bone strength and mass characterizing osteoporosis. The present work provides an overview of the current knowledge of the pathophysiology of osteoporosis obtained through advances in epigenetics, cell biology and osteoimmunology. In light of the increasingly recognized importance of bone-muscle interconnection, this review also discusses relevant pathways that may be dissected for identifying new therapeutic targets for age-related musculoskeletal degeneration.

The Impact of Type 2 Diabetes on Bone Fracture Healing.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease known by the presence of elevated blood glucose levels. Nowadays, it is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Many are the complications caused by this chronic disorder, including a negative impact on the cardiovascular system, kidneys, eyes, muscle, blood vessels, and nervous system. Recently, there has been increasing evidence suggesting that T2DM also adversely affects the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. Nevertheless, the precise mechanisms by which T2DM causes detrimental effects on bone tissue are still elusive and remain poorly studied. The aim of this review was to synthesize current knowledge on the different factors influencing the impairment of bone fracture healing under T2DM conditions. Here, we discuss new approaches used in recent studies to unveil the mechanisms and fill the existing gaps in the scientific understanding of the relationship between T2DM, bone tissue, and bone fracture healing.

Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.

Plasma Citrate Homeostasis: How It Is Regulated; And Its Physiological and Clinical Implications. An Important, But Neglected, Relationship in Medicine

The homeostatic maintenance of a normal plasma citrate concentration is an important factor in humans and in animals; and is required for many normal physiological activities. Dysregulation of normal plasma citrate presents pathophysiological hypocitricemic or hypercitricemic conditions. This can lead to clinical consequences in many areas of medicine; such as impaired blood clotting, altered acid/base status, impaired neuromuscular/cardiac activities, hypocitraturia and stone formation, bone disorders with loss of bone strength and increased fractures, hypocitricemia of surgical stress. These important implications of citrate relationships have been largely ignored by the contemporary clinical and biomedical community; to the extent that it is not even described in most current textbooks and review papers. This review describes the physiological, endocrine, and metabolic relationships in the normal regulation and maintenance of plasma citrate; and presents some important clinical consequences of its dysfunctional maintenance. The importance of bone, kidney and liver activities in the maintenance of normal plasma citrate is described along with the citricemic roles of parathyroid hormone, calcitonin and vitamin D. These factors and relationships are presented as the contemporary understanding of the integrated regulation of plasma citrate as the basis for its clinical importance in medicine. The exclusion of these citrate relationships leads to misunderstanding and misrepresentation of physiological and clinical conditions in many issues in medicine and paramedicine areas. The intent of this review is to revive the interest and support for research to address the many unknown and speculative issues of plasma citrate regulation and its important clinical implications. This is in the best interest of the medical community and the public-at-large.

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased.Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (−55% vs. Pregnant, p<0.01), BV/TV (−40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (−29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss.

Dynamic modeling of bone metastasis, microenvironment and therapy: Integrating parathyroid hormone (PTH) effect, anti-resorptive and anti-cancer therapy

Bone is a common site for the development of metastasis, as its microenvironment provides the necessary conditions for the growth and proliferation of cancer cells. Several mathematical models to describe the bone remodeling process and how osteoclasts and osteoblasts coupled action ensures bone homeostasis have been proposed and further extended to include the effect of cancer cells. The model proposed here includes the influence of the parathyroid hormone (PTH) as capable of triggering and regulating the bone remodeling cycle. It also considers the secretion of PTH-related protein (PTHrP) by cancer cells, which stimulates the production of receptor activator of nuclear factor kappa-B ligand (RANKL) by osteoblasts that activates osteoclasts, increasing bone resorption and the subsequent release of growth factors entrapped in the bone matrix, which induce tumor growth, giving rise to a self-perpetuating cycle known as the vicious cycle of bone metastases. The model additionally describes how the presence of metastases contributes to the decoupling between bone resorption and formation. Moreover, the effects of anti-cancer and anti-resorptive treatments, through chemotherapy and the administration of bisphosphonates or denosumab, are also included, along with their corresponding pharmacokinetics (PK) and pharmacodynamics (PD). The simulated models, available at http://sels.tecnico.ulisboa.pt/software/, are able to describe bone remodeling cycles, the growth of bone metastases and how treatment can effectively reduce tumor burden on bone and prevent loss of bone strength.

Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven

ObjectiveAlthough osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats. MethodsBones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD. ResultsHLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density. ConclusionsHLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats.

Development and implementation of a coupled computational muscle force optimization bone shape adaptation modeling method.

Improved methods to analyze and compare the muscle-based influences that drive bone strength adaptation can aid in the understanding of the wide array of experimental observations about the effectiveness of various mechanical countermeasures to losses in bone strength that result from age, disuse, and reduced gravity environments. The coupling of gradient-based and gradientless numerical optimization routines with finite element methods in this work results in a modeling technique that determines the individual magnitudes of the muscle forces acting in a multisegment musculoskeletal system and predicts the improvement in the stress state uniformity and, therefore, strength, of a targeted bone through simulated local cortical material accretion and resorption. With a performance-based stopping criteria, no experimentally based or system-based parameters, and designed to include the direct and indirect effects of muscles attached to the targeted bone as well as to its neighbors, shape and strength alterations resulting from a wide range of boundary conditions can be consistently quantified. As demonstrated in a representative parametric study, the developed technique effectively provides a clearer foundation for the study of the relationships between muscle forces and the induced changes in bone strength. Its use can lead to the better control of such adaptive phenomena.

Management of postmenopausal osteoporosis.

A hallmark of menopause, which follows the decline in the ovarian production of estrogen, is the aggressive and persistent loss of bone mineral and structural elements leading to loss of bone strength and increased fracture risk. This review focuses on newer methods of diagnosing osteoporosis and assessing fracture risk, as well as on novel management strategies for prevention and treatment. Fracture-risk prediction has been significantly enhanced by the development of methods such as the trabecular bone score, which helps assess bone microarchitecture and adds value to standard bone densitometry, and the Fracture Risk Assessment Tool (FRAX) algorithm techniques. The treatment of osteoporosis, which has the goals of fracture prevention and risk reduction, is moving beyond traditional monotherapies with antiresorptives and anabolic agents into new combination regimens.

Zoledronate prevents lactation induced loss of bone strength and micro-architecture

Zoledronate prevents lactation induced loss of bone strength and micro-architecture

TGFβ Inducible Early Gene-1 Plays an Important Role in Mediating Estrogen Signaling in the Skeleton

TGFβ Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a sex-specific osteopenic phenotype characterized by low bone mineral density, bone mineral content, and overall loss of bone strength in female mice. We, therefore, speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. To test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell, and biochemical level. Dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter and resorptive activity as determined by serum levels of CTX-1 were differentially regulated after estrogen treatment in TIEG1 KO mice compared with wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the sex-specific osteopenic phenotype observed in female TIEG1 KO mice.

La vitamine D en pédiatrie

Infantile Nutritional Rickets has disappeared almost completely in France since 1992 as vitamin D enriched formula availability and previous vitamin D supplementation of infants. The search of evocative symptoms of rickets should be a routine procedure in infants, in particular in case of insufficient vitamin D intake i.e. breastfeeding, and the possibility of vitamin D resistant rickets. Hypocalcaemia occurs not only at the first but also the advanced stages of vitamin D deficiency, and may be responsible for severe cardiologic, neurologic or respiratory complications with possibility of infant death. For the young children between 1 and 5 years and for adolescents, vitamin D insufficiency is responsible for poor skeletal mineralization, loss of bone strength, and a reduction of peak of bone mineral mass at the end of puberty. The new Dietary Reference Intakes (DRI, 2011) increased greatly the Recommended Dietary allowances (RDA) from 200 to 600 IU/d (15 μg/d) for individuals from 1 to 70 years of age. These levels are not reached in winter, even in countries, like USA and Canada, where vitamin D milk fortification is mandatory and others like Japan and North-European countries despite high fish consumption. From 1 to 5 years of age and during adolescence, a winter vitamin D3 supplementation is necessary with 80.000 or 100.000 IU periodic loads every 3 months i.e. in November and February. In cases of an underlying risk, i.e. insufficient vitamin D photosynthesis in summertime (dark skin, wearing heavily skin-covering clothes, or several skin diseases), or digestive, renal or nutritional pathologies, use of some drugs, loading dose of 80.000 or 100.000 IU, every 3 months should be administered over the year.

AB0528 Bone mineral density, vertebral fractures and their determinants in ankylosing spondylitis

BackgroundOsteoporosis responsible for loss of bone strength and vertebral fracture (VF) rates ranged from 0% to 18% have been reported in patients with ankylosing spondylitis (AS).ObjectivesIn this study we examined...

Kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fractures

Background The incidence of osteoporotic vertebral compression fractures increases with advancing age and is associated with significant healthcare expenditure. Patients who have sustained fractures from osteoporosis are at increased risk of additional fractures because of loss of bone strength caused by osteoporosis. Vertebroplasty is a minimally invasive vertebral augmentation procedure to relieve pain; it stabilizes the vertebral body. Kyphoplasty is a minimally invasive method for correction and augmentation of osteoporotic vertebral fractures. Materials and methods This study included two groups of patients suffering from painful osteoporotic vertebral compression fractures: the first group comprised 26 patients with 33 vertebral compression fractures treated by percutaneous vertebroplasty between April 2007 and October 2008. The results of this group were compared with those of another group of 18 patients (24 vertebrae) who were treated by kyphoplasty between November 2008 and July 2011. The visual analog scale (VAS) and the Oswestry Disability Index (ODI) were applied for the assessment of patients preoperatively and postoperatively. Results In the vertebroplasty group, the mean VAS score improved from 7.8 to 2.4 according to VAS and from 69 to 15 according to ODI. Cement leakage was noted in four patients (15.4%), without clinical consequence. Ten vertebrae (30.3%) revealed a mean improvement in vertebral height of 11% (8–14%). No patient showed progression of vertebral angles of the augmented vertebrae during the follow-up period. In the kyphoplasty group, the mean pain score improved from 8 to 2.1 according to VAS and from 71 to 17 according to ODI. Cement leakage was noted in two patients (11.11%), without clinical consequence. No thoracolumbar back pain was reported after kyphoplasty. Nineteen vertebrae (79.16%) revealed a mean improvement in vertebral height of 22% (range, 18–38%). No patient showed progression of vertebral angles of the augmented vertebrae during the follow-up period. Conclusion Both vertebroplasty and kyphoplasty resulted in significant improvement in VAS pain scores. Vertebroplasty, although less expensive than kyphoplasty, had a statistically greater risk for cement leakage and adjacent vertebral fracture.

Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator

Selective androgen receptor modulators (SARMs) are androgens with tissue-selective activity. SARMs that have anabolic activity on muscle while having minimal stimulatory activity on prostate are classified as SARM agonists. They can be used to prevent the loss of lean body mass that is associated with cancer, immunodeficiency, renal disease and aging. They may also have anabolic activity on bone; thus, unlike estrogens, they may reverse the loss of bone strength associated with aging or hypogonadism. Our in-house effort on SARM program discovers a nonsteroidal androgen receptor ligand with a unique imidazolopyrazole moiety in its structure. In vitro, this compound is a weak androgen receptor binder and a weak androgen agonist. Despite this, in orchidectomized mature rats it is an effective SARM agonist, with an ED50 on levator ani muscle of 3.3mg/kg and an ED50 on ventral prostate of >30mg/kg. It has its maximal effect on muscle at the dose of 10mg/kg. In addition, this compound has mixed agonistic and antagonistic activities on prostate, reducing the weight of that tissue in intact rats by 22% at 10mg/kg. The compound does not have significant effect on gonadotropin levels or testosterone levels in both orchidectomized and intact male rats. It does not have notable progestin, estrogen or glucocorticoid agonistic or antagonistic activity in rats. In a female sexual behavior model, it improves the sexual desire of ovariectomized female rats for sexually mature intact males over nonsexually ovariectomized females. Overall, the imidazolopyrazole is a potent prostate-sparing candidate for development as a SARM agonist with an appropriate pharmacological profile for clinical benefit in muscle-wasting conditions and female sexual function disorders.

Combined activation of PPAR-gamma and PPAR-alpha reduces the negative effects of PPAR-gamma agonism on bone and may attenuate PPAR-gamma-mediated loss of bone strength

Combined activation of PPAR-gamma and PPAR-alpha reduces the negative effects of PPAR-gamma agonism on bone and may attenuate PPAR-gamma-mediated loss of bone strength

Combined activation of PPAR-gamma and PPAR-alpha reduces the negative effects of PPAR-gamma agonism on bone and may attenuate PPAR-gamma-mediated loss of bone strength

Combined activation of PPAR-gamma and PPAR-alpha reduces the negative effects of PPAR-gamma agonism on bone and may attenuate PPAR-gamma-mediated loss of bone strength