Reduced Bone Quality Research Articles

Bone turnover markers to assess jawbone quality prior to dental implant treatment: a case-control study

BackgroundBone quality is as important as bone mineral density in terms of bone strength. Bone turnover markers (BTMs) are clinical indicators of bone quality. In implant dentistry, bone quality is considered equivalent to bone density on radiographic assessments. The purpose of this study was to determine whether the BTM values are reflected in jawbone condition by evaluating the relationship at baseline and during follow-up in patients with prosthodontic implants.Computed tomography (CT) scans were obtained and BTM (osteocalcin, bone-specific alkaline phosphatase, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and crosslinked N-telopeptide of type I collagen) levels in blood samples were measured in partially edentulous eighteen patients before implant surgery. During the follow-up observation after implant surgery, marginal bone loss (MBL) was measured on dental radiography. We investigated the relationship between the presence of BTM abnormalities and radiographic bone density.ResultsMore women than men had abnormal BTM values. Bone turnover was accelerated in the group of women with abnormal BTM values. The density of cancellous bone at the implant placement site was significantly lower in the patients with abnormally high BTM values than in their counterparts with BTM values in the normal range.ConclusionsFemale patients who undergo implant treatments may have reduced bone quality; evaluations of bone strength will require assessments of both BTMs and the density of cancellous bone.

Exposure to high levels of magnesium disrupts bone mineralization in vitro and in vivo.

BackgroundThe removal of permanent internal fixation devices by secondary surgery could be avoided if these devices were made of degradable magnesium and magnesium alloys. Before such implants can be used clinically, however, the biological effect of magnesium exposure on surrounding bone must be evaluated. Previous studies have focused on bone formation; few have examined the effects of magnesium on the bone quality that affect many biomechanical properties.MethodsUsing bone quality parameters, we analyzed in vivo changes in bone properties and biomechanics after exposure to locally high levels of magnesium.ResultsLocal bone mineralization was significantly disrupted following exposure to a porous rod of pure magnesium. Normal crystal formation and crystallinity were inhibited and the mineral-to-matrix ratio decreased. These results were consistent with those of in vitro experiments, in which high levels of magnesium inhibited mineral deposition by mesenchymal stem cells (MSCs) but increased alkaline phosphatase (ALP) expression. The same mineralization inhibition was observed around magnesium implants via micro-computerized tomography (micro-CT) and von Kossa staining. Such reduced bone quality around degrading magnesium rods could negatively impact bone biomechanics.ConclusionsThis study showed that exposure to the local high magnesium levels that arise from rapidly degrading magnesium devices may significantly disrupt bone mineralization and negatively impact bone biomechanics.

Cortical threaded pedicle screw improves fatigue strength in decreased bone quality

PurposeInadequate anchoring of pedicle screws in vertebrae with poor bone quality is a major problem in spine surgery. The aim was to evaluate whether a modified thread in the area of the pedicle could significantly improve the pedicle screw fatigue strength.MethodsFourteen human cadaveric vertebral bodies (L2 and L3) were used for in vitro testing. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by standard pedicle screws with a constant double thread on the right pedicle and a partial doubling of the threads–quad thread–(cortical thread) in the area of the pedicle on the left pedicle. Pulsating sinusoidal, cyclic load (0.5 Hz) with increasing peak force (100 N + 0.1 N/cycles) was applied orthogonal to the screw axis. The baseline force remained constant (50 N). Fatigue test was terminated after exceeding 5.4-mm head displacement (~ 20° screw tilting).ResultsThe mean fatigue load at failure was 264.9 N (1682 cycles) for the standard screws and was increased significantly to 324.7 N (2285 cycles) by the use of cortical threaded screws (p = 0.014). This effect is particularly evident in reduced BMD (standard thread 241.2 N vs. cortical thread 328.4 N; p = 0.016), whereas in the group of vertebrae with normal BMD no significant difference could be detected (standard thread 296.5 N vs. cortical thread 319.8 N; p = 0.463).ConclusionsCompared to a conventional pedicle screw, the use of a cortical threaded pedicle screw promises superior fatigue load in vertebrae with reduced bone quality.

Bisphosphonates and parathyroid hormone analogs for improving bone quality in spinal fusion: State of evidence.

Spinal fusion is among the most commonly performed surgical procedures for elderly patients with spinal disorders – including degenerative disc disease with spondylolisthesis, deformities, and trauma. With the large increase in the aging population and the prevalence of osteoporosis, the number of elderly osteoporotic patients needing spinal fusion has risen dramatically. Due to reduced bone quality, postoperative complications such as implant failures, fractures, post-junctional kyphosis, and pseudarthrosis are more commonly seen after spinal fusion in osteoporotic patients. Therefore, pharmacologic treatment strategies to improve bone quality are commonly pursued in osteoporotic cases before conducting spinal fusions. The two most commonly used pharmacotherapeutics are bisphosphonates and parathyroid hormone (PTH) analogs. Evidence indicates that using bisphosphonates and PTH analogs, alone or in combination, in osteoporotic patients undergoing spinal fusion, decreases complication rates and improves clinical outcomes. Further studies are needed to develop guidelines for the administration of bisphosphonates and PTH analogs in osteoporotic spinal fusion patients in terms of treatment duration, potential benefits of sequential use, and the selection of either therapeutic agents based on patient characteristics.

Controversy of physiological vs. pharmacological effects of BMP signaling: Constitutive activation of BMP type IA receptor-dependent signaling in osteoblast lineage enhances bone formation and resorption, not affecting net bone mass.

Bone morphogenetic proteins (BMPs) were first described over 50years ago as potent inducers of ectopic bone formation when administrated subcutaneously. Preclinical studies have extensively examined the osteoinductive properties of BMPs in vitro and new bone formation in vivo. BMPs (BMP-2, BMP-7) have been used in orthopedics over 15years. While osteogenic function of BMPs has been widely accepted, our previous studies demonstrated that loss-of-function of BMP receptor type IA (BMPR1A), a potent receptor for BMP-2, increased net bone mass by significantly inhibiting bone resorption in mice, indicating a positive role of BMP signaling in bone resorption. The physiological role of BMPs (i.e. osteogenic vs. osteoclastogenic) is still largely unknown. The purpose of this study was to investigate the physiological role of BMP signaling in endogenous long bones during adult stages. For this purpose, we conditionally and constitutively activated the Smad-dependent canonical BMP signaling thorough BMPR1A in osteoblast lineage cells using the mutant mice (Col1CreER™:caBmpr1a). Because trabecular bones were largely increased in the loss-of-function mouse study for BMPR1A, we hypothesized that the augmented BMP signaling would affect endogenous trabecular bones. In the mutant bones, the Smad phosphorylation was enhanced within physiological level three-fold while the resulting gross morphology, bodyweights, bone mass/shape/length, serum calcium/phosphorus levels, collagen cross-link patterns, and healing capability were all unchanged. Interestingly, we found; 1) increased expressions of both bone formation and resorption markers in femoral bones, 2) increased osteoblast and osteoclast numbers together with dynamic bone formation parameters by trabecular bone histomorphometry, 3) modest bone architectural phenotype with reduced bone quality (i.e. reduced trabecular bone connectivity, larger diametric size but reduced cortical bone thickness, and reduced bone mechanical strength), and 4) increased expression of SOST, a downstream target of the Smad-dependent BMPR1A signaling, in the mutant bones. This study is clinically insightful because gain-of-function of BMP signaling within a physiological window does not increase bone mass while it alters molecular and cellular aspects of osteoblast and osteoclast functions as predicted. These findings help explain the high-doses of BMPs (i.e. pharmacological level) in clinical settings required to substantially induce a bone formation, concurrent with potential unexpected side effects (i.e. bone resorption, inflammation) presumably due to a broader population of cell-types exposed to the high-dose BMPs rather than osteoblastic lineage cells.

Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat.

Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.

Cartilage -specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency.

Spontaneous catch-up (CU) growth occurs when a growth-restricting factor is resolved. However, its efficiency is sometimes inadequate and growth deficits remain permanent. The therapeutic toolbox for short stature is currently very limited, thus, finding new regulatory pathways is important for the development of novel means of treatment. Our previous studies using a nutrition-induced CU growth model showed that the level of sirtuin-1 (Sirt1) was significantly increased in food-restricted animals and decreased during CU growth. This study sought to investigate the role of Sirt1 in modulating the response of the epiphyseal growth plate (EGP) to nutritional manipulation. Collagen type II-specific Sirt1 knockout (CKO) mice were tested for response to our CU growth model consisting of a period of food restriction followed by re-feeding. The transgenic CKO mice weighed more than the control (CTL) mice, their EGP was higher and less organized, specifically at the resting and proliferative zones, leading to shorter bones. Ablation of Sirt1 in the chondrocytes was found to have a dramatic effect on bone mineralization on micro-CT analysis. The CKO mice were less responsive to the nutritional manipulation, and their CU growth was less efficient. They remained shorter than the CTL mice who corrected the food restriction-induced growth deficit during the re-feeding period. Sirt1 appears to be important for normal regulation of the EGP. In its absence, the EGP is less organized and CU growth is less efficient. These results suggest that SIRT1 may serve as a novel therapeutic target for short stature.

Osseodensification Drilling vs. Standard Protocol of Implant Site Preparation: An In Vitro Study on Polyurethane Foam Sheets

(1) Background: The aim of the present in vitro investigation was to evaluate, on polyurethane sheets, two different drilling techniques for dental implant positioning using osteocondensing burs compared to a standard type protocol. (2) Methods: Three different implant designs (Implacil De Bortoli UN III 4 × 10 mm, Restore RBM 4 (HEX) × 10 mm; Implacil De Bortoli UN II 4 × 10 mm) were evaluated (test implant (osteocondensing drills) and control implant (standard drills)). The insertion torque (IT), the removal torque (RT) and the resonance frequency analysis (RFA) values of test and control implants inserted in different size and different density polyurethane foam models were compared for 120 experimental sites. Accordingly, 120 experimental holes were produced in different PCF polyurethane foams: 60 sites were produced in 10 PCF sheets and 60 sites in 10 PCF sheets with an additional 1 mm layer of 30 PCF. (3) Results: The IT, removal torque and RFA values were significantly higher for both of the evaluated implants, in the sites prepared with the osteocondenser drills when compared to sites prepared with standard drills (p < 0.05). The UNII and UN III showed significantly higher stability compared to the HEX implant; these differences increased drastically in the 10 PCF Polyurethane Block with the additional 1 mm cortical layer (p < 0.05). (4) Conclusions: The outcome of this investigation suggested a possible clinical application of osteocondensing burs in case of reduced bone quality and quantity in the posterior maxilla.

Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna

Aging is known to reduce bone quality and bone strength. We sought to determine how aging affects the biomechanical and architectural properties of various long bones, and if sex influences age related differences/changes. While researchers have extensively studied these changes in individual bones of mice, there is no comprehensive study of the changes in the bones from the same mice to study the changes with aging. We performed three point bending tests and microcomputed tomography (microCT) analysis on femurs, tibiae and ulnae. Three point bending tests were utilized to calculate biomechanical parameters and imaging was also performed using high resolution microCT to reveal both cortical and trabecular microarchitecture C57BL/6N mice were divided into three age groups: 6, 12 and 22 months. Each age and sex group consisted of 6–7 mice. The ultimate load to failure (UL), elastic stiffness (ES), modulus of elasticity (E) and the moment of inertia about bending axis (MOI) for each bone was calculated using three point bending test. MicroCT scans of all the bones were analyzed to determine cortical bone volume per tissue volume (C.BV/TV), trabecular bone volume per tissue volume (Tb.BV/TV), cortical bone area (B.Ar) using CTAn's microCT analysis and tested for correlation with the biomechanical parameters. Mean (standard error) values of UL in femur decreased from 19.8(0.6) N to 12.8(1.1) N (p < .01) and 17.9(0.6) N to 14.6(1.0) N (p = .02) from 6 to 22 months groups in males and females respectively. Similarly, UL in tibia decreased from 19.8(0.5) N to 14.3(0.2) N (p < .01) and 14.4(0.6) N to 9.5(1.0) N (p < .01) from 6 to 22 months group in males and females respectively. ES in femur decreased from 113.2(7) N/mm to 69.6(6.7) N/mm (p < .01) from 6 to 22 months in males only. ES in tibia decreased from 78.6(3.2) N/mm to 65.0(2.3) N/mm (p = .01) and 53.1(2.9) N/mm to 44.0(1.7) N/mm (p = .02) from 6 to 22 months in males and females respectively. Interestingly, ES in ulna increased from 8.2(0.8) N/mm to 10.9(1.0) N/mm (p = .051) from 6 to 22 months of age in females only. E in femur decreased from 4.0(0.4) GPa to 2.8(0.2) GPa (p = .01) and 6.7(0.5) GPa to 4.5(0.4) GPa (p = .01) from 6 to 22 months of age in males and females respectively while tibia showed no change. However, E in ulna increased from 7.0(0.8) GPa to 11.0(1.1) GPa (p = .01) from 6 to 22 months of age in females only. Changes in age and sex-related bone properties were more pronounced in the femur and tibia, while the ulna showed fewer overall differences. Most of the changes were observed in biomechanical compared to architectural properties and female bones are more severely affected by aging. In conclusion, our data demonstrate that care must be taken to describe bone site and sex-specific, rather than making broad generalizations when describing age-related changes on the biomechanical and architectural properties of the skeleton.

Cement augmentation of an angular stable plate osteosynthesis for supracondylar femoral fractures - biomechanical investigation of a new fixation device

BackgroundImplant anchorage in highly osteoporotic bone is challenging, since it often leads to osteosynthesis failure in geriatric patients with supracondylar femoral fractures. Cementation of screws is presumed to prevent such osteosynthesis failure. This study aimed to investigate the effect of a newly designed, cementable fenestrated condylar screw for plate fixation in a biomechanical setting.MethodsEight pairs of osteoporotic cadaver femora with an average age of 77 years, ranging between 62 and 88 years, were randomly assigned to either an augmented or a non-augmented group. In both groups an instable 33-A3 fracture according to the AO / OTA classification was fixed with an angular stable locking plate. All right samples received a cement augmentation of their fenestrated condylar screws with calcium phosphate bone cement (CPC). Mechanical testing was performed at a load to failure mode by cyclic axial loading, using a servohydraulic testing machine.ResultsWith a mean of 2475 N (95% CI: 1727–3223 N), the pressure forces resulting in osteosynthesis failure were significantly higher in specimen with cemented condylar screws as compared to non-cemented samples (1875 N (95% CI: 1320–2430 N)) (p = 0.024). In both groups the deformation of the constructs, with the distal screws cutting through the condylar bone, were the most frequent cause for failure. Analysis of axial stiffness (p = 0.889) and irreversible deformity of the specimens revealed no differences between the both groups (p = 0.161). No cement leakage through the joint line or the medial cortex was observed.ConclusionBased on the present study results, the newly introduced, cementable condylar screw could be an encouraging feature for the fixation of supracondylar femoral fractures in patients with reduced bone quality in terms of load to failure accuracy of the cement application.

Management of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is the term used to describe a group of rare inherited skeletal disorders characterized by a greatly increased risk of fragility fractures (1). Mutations in several genes can cause OI but the condition is most commonly caused by mutations of COLIA1 or COL1A2 resulting in the production of collagen which is abnormal or present in reduced amounts. Fractures in OI are particularly common during childhood but the elevated fracture risk continues throughout life. Bone mineral density (BMD) can be reduced in OI but the magnitude of increase in fracture risk is far greater than can be accounted for by low BMD, highlighting that a key mechanism of bone fragility is reduced bone quality due to defects of bone matrix and mineralization. A multidisciplinary approach is needed to optimize management of OI, with input from physicians, orthopedic surgeons, physiotherapists, occupational therapists, and other allied health professionals. Orthopedic surgery plays a key role both in the fixation of fractures and in the correction of limb deformities. Bisphosphonates have been widely used in the treatment of children and adults with OI. Although there is good evidence that they increase BMD, it is uncertain to what extent they reduce fracture risk. Clinical trials of bone anabolic drugs such as teriparatide and inhibitors of sclerostin have also been studied; although they increase BMD, studies of these agents have not been powered to look at fracture endpoints. Various other treatment modalities including denosumab, and cell therapy have been explored but haven't gained acceptance in routine clinical practice. There have been huge advances in understanding the pathogenesis of OI but these have not been accompanied by advances in treatment. This signals need for well-designed clinical trials with fracture endpoints in OI, both with existing agents and with the newer therapeutic agents that are now starting to emerge.

A New Diagnostic Approach for Periprosthetic Acetabular Fractures Based on 3D Modeling: A Study Protocol.

Periprosthetic acetabular fractures after total hip arthroplasty (THA) are mostly related to low energy trauma reduced bone quality. CT-scan is widely used to evaluate acetabular fractures, however, metal artifacts produced prosthetic implants limit the visualization of the articular surface and bone loss assessment. 3D modeling software allows us to creating tridimensional images of the bony surface, removing the metallic implants trough image segmentation. We highlight the use of 3D modeling and rapid prototyping (3D printing) for the diagnostic process of periprosthetic acetabular fracture around THA. 3D modeling software was used to improve the assessment of fracture morphology and bone quality. Moreover, the 3D images were printed in a real-life size model and used for preoperative implant templating, sizing and surgical simulation.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6kg/m2; median age 57, range 50-69years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2=0.23; β=0.03; p=0.044) and higher radius cortical BMD (R2=0.43; β=8.4; p=0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2=0.38; β=0.96; p=0.050), higher radius trabecular number (R2=0.31; β=0.01; p=0.026), lower tibia and radius trabecular separation (tibia: R2=0.30; β=-0.003; p=0.038; radius: R2=0.35; β=-0.003; p=0.021), and higher radius bone stiffness (R2=0.45; β=0.38; p=0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2=0.44; β=4.06; p=0.036), higher tibia bone stiffness (R2=0.46; β=3.06; p=0.050), and higher tibia estimated failure load (R2=0.46; β=0.17; p=0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2=0.39; β=-41.2; p=0.042), lower radius trabecular number (R2=0.34; β=-0.44; p=0.009) and greater radius trabecular separation (R2=0.42; β=0.16; p=0.002), while TDF use without a PI was not associated with reduced bone quality. In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Bone Mineral Is More Heterogeneously Distributed in the Femoral Heads of Osteoporotic and Diabetic Patients: A Pilot Study.

ABSTRACTOsteoporosis is associated with systemic bone loss, leading to a significant deterioration of bone microarchitecture and an increased fracture risk. Although recent studies have shown that the distribution of bone mineral becomes more heterogeneous because of estrogen deficiency in animal models of osteoporosis, it is not known whether osteoporosis alters mineral distribution in human bone. Type 2 diabetes mellitus (T2DM) can also increase bone fracture risk and is associated with impaired bone cell function, compromised collagen structure, and reduced mechanical properties. However, it is not known whether alterations in mineral distribution arise in diabetic (DB) patients’ bone. In this study, we quantify mineral content distribution and tissue microarchitecture (by μCT) and mechanical properties (by compression testing) of cancellous bone from femoral heads of osteoporotic (OP; n = 10), DB (n = 7), and osteoarthritic (OA; n = 7) patients. We report that though OP cancellous bone has significantly deteriorated compressive mechanical properties and significantly compromised microarchitecture compared with OA controls, there is also a significant increase in the mean mineral content. Moreover, the heterogeneity of the mineral content in OP bone is significantly higher than controls (+25%) and is explained by a significant increase in bone volume at high mineral levels. We propose that these mineral alterations act to exacerbate the already reduced bone quality caused by reduced cancellous bone volume during osteoporosis. We show for the first time that cancellous bone mineralization is significantly more heterogeneous (+26%) in patients presenting with T2DM compared with OA (non‐DB) controls, and that this heterogeneity is characterized by a significant increase in bone volume at low mineral levels. Despite these mineralization changes, bone microarchitecture and mechanical properties are not significantly different between OA groups with and without T2DM. Nonetheless, the observed alterations in mineral heterogeneity may play an important tissue‐level role in bone fragility associated with OP and DB bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Good long-term glycemic compensation is associated with better trabecular bone score in postmenopausal women with type 2 diabetes.

Osteoporosis is an increasingly widespread disease, as well as diabetes mellitus. It is now accepted that osteoporotic fractures are a serious co-morbidity and complication of diabetes. Despite of good bone mineral density in Type 2 Diabetes (T2DM) patients is the fracture risk elevated. It is due to reduced bone quality. To determine the effect of glycemic compensation on bone density and trabecular bone score (TBS) in T2DM. We analyzed a cohort of 105 postmenopausal women with T2DM. For all patients, central bone density (spinal and lumbar spine) was tested by DXA methodology, glycemic control parameters were assessed, and anthropometric parameters were measured. Bone quality was analyzed using TBS software. The results were statistically processed. Good glycemic compensation with glycated hemoglobin (A1c) value <7.0 % DCCT did not lead to BMD changes in patients with T2DM. However, patients with HbA1c <7 % DCCT had significantly better TBS (1.254±0.148 vs. 1.166±0.094, p=0.01). There was a negative correlation between TBS and glycated hemoglobin (r= -0,112, p<0.05) with glycemic fasting (r= -0.117, p<0.05). The optimal effect on TBS is achieved when all three markers of glycemic compensation (glycated hemoglobin, fasting plasma glucose and postprandial glycemia) are in optimal range. By using ROC curves glycated hemoglobin has the most significant effect on TBS. Optimal glycemic compensation, evaluated by glycated hemoglobin, does not lead to changes in BMD but has a beneficial effect on TBS in T2DM. Good glycemic control is required also for reduction of the risk of osteoporosis and osteoporotic fractures.

Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in type 2 diabetes: study protocol for a randomised clinical trial

IntroductionType 2 diabetes (T2D) is associated with an increased fracture risk despite normal-to-increased bone mineral density, suggesting reduced bone quality. Exercise may be effective in reducing fracture risk by ameliorating...

Clinical pathologies of bone fracture modelled in zebrafish.

ABSTRACTReduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The csf1ra mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with Staphylococcus aureus, neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput.This article has an associated First Person interview with the first author of the paper.

Diabetic Skeletal Health and Potential Benefits of Exercise

ABSTRACT Bone tissue undergoes continual remodeling through resorption and formation. The balance between these 2 activities is critical to optimizing bone mineral density (BMD) and the biomechanical integrity of the tissue, thereby reducing fractures. There is increasing evidence that diabetes negatively alters the cellular activity of bone tissue and reduces bone quality resulting in an increased risk of fractures. The mechanisms by which diabetes impacts bone are not completely understood; however, insulin, hyperglycemia, and glycation appear to influence skeletal regulation. This review will explore the influence of diabetes mellitus on bone as well as examine the potential methods by which exercise can serve as a nonpharmacological method to optimize bone health in persons with diabetes.

SUN-292 BENEFITS AND HARMS OF VITAMIN D COMPOUNDS IN ADULTS WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS

Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) is a systemic disorder characterised by vitamin D deficiency, elevated parathyroid hormone (PTH) levels, reduced bone quality, and increased fracture risk. Vitamin D therapy is an essential part of the CKD-MBD management. This systematic review was performed to study the effects of vitamin D therapy on fractures, mortality, bone mineral density (BMD), and biochemical markers of CKD-MBD.

Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were not clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. These findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.