Changes In Bone Remodeling Research Articles

PTH and bone material strength in hypoparathyroidism as measured by impact microindentation.

PTH is a key regulator of bone structure and remodeling. When PTH is absent in hypoparathyroidism (HypoPT), bone mass is increased and remodeling is decreased. In addition to bone structure and remodeling, bone material properties contribute to fracture resistance. Yet little is known about the relationship between PTH and bone material properties. Impact microindentation provides a clinical assessment of microfracture resistance, measured as the bone material strength index (BMSi). Case-control cross-sectional study of PTH levels and in vivo BMSi measurement by impact microindentation at the anterior tibia in HypoPT patients (n = 17) and in controls matched for age, sex, and menopausal status (n = 17), with follow-up in a subgroup of HypoPT patients (n = 5) after recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] treatment. BMSi was positively associated with PTH levels in controls (r = 0.58, p = 0.02) and was 11% lower (p = 0.01) in HypoPT patients as compared with controls. In HypoPT, lower BMSi was associated with a trend toward greater supplemental calcium doses (p = 0.07). BMSi increased after rhPTH(1-84) treatment in the HypoPT patients who underwent repeat microindentation. PTH levels might be associated with bone material strength, although other factors might be contributory. In HypoPT, resistance to microfracture is decreased and may be associated with greater supplemental calcium doses and might increase with PTH replacement. It remains to be determined whether changes in bone remodeling and microarchitecture contribute to the effects of PTH on microfracture resistance.

The influence of the Pilates method on quality of life and bone remodelling in older women: a controlled study.

The objective of this study was to evaluate the effects of the Pilates method on quality of life and bone remodeling markers in a group of older women. A longitudinal prospective study with intervention was performed on 40 women aged over 60years; they were divided into two groups: one submitted to a 50-min Pilates exercise session once a week for 20weeks (Pilates), and the other was not (Control). Both groups were compared for quality of life using the Medical Outcomes Study 36, and for bone-specific alkaline phosphatase (BSAP) and Type 1 collagen C-telopeptide (CTx) bone remodeling markers. The Pilates group presented improvement in the quality of life evaluation scores: physical functioning (67.50 ± 18.88 × 86.25 ± 9.58; p = 0.0232), and physical component summary (65.00 ± 14.39 × 79.70 ± 3.83; p = 0.0220). The Pilates group also presented higher scores than that of Controls after the exercise program: physical functioning (86.25 ± 9.58 × 55.50 ± 20.83, p = 0.0003), physical role (100.00 ± 0.00 × 41.25 ± 46.79, p = 0.0009), emotional role (100.00 ± 0.00 × 48.33 ± 50.12, p = 0.0046), vitality (82.50 ± 14.28 × 60.25 ± 21.43, p = 0.011), physical component summary (79.70 ± 3.83 × 54.90 ± 15.05, p < 0.0001), and emotional component summary (74.10 ± 8.37 × 54.18 ± 22.55, p = 0.0111). No changes were noted in bone remodeling markers [CTx (0.39 ± 0.26 × 0.38 ± 0.22ng/mL) and BSAP (10.73 ± 2.40 × 11.01 ± 3.56μg/L)] and did not differ from the Control group both before (CTx: 0.39 ± 0.26 × 0.37 ± 0.17ng/mL; BSAP: 10.73 ± 2.40 × 10.58 ± 3.49μg/L; p > 0.05) and after exercise (CTx: 0.38 ± 0.22 × 0.38 ± 0.22ng/mL; BSAP: 11.01 ± 3.56 × 9.85 ± 3.12μg/L; p > 0.05). The group of women submitted to Pilates presented improved quality of life but without changes in bone remodeling.

Mandibular Cortical Bone Loss Early after Definitive Chemoradiotherapy for Oropharyngeal Squamous Cell Carcinoma

Patients receiving radiotherapy (RT) for oropharyngeal carcinoma are at risk of mandibular toxicity. Risk factors include RT dose exceeding 60 Gy, local trauma, and uncontrolled periodontal disease. Treatment-related osteonecrosis is likely due to changes in bone remodeling. We aim to identify longitudinal changes in mandibular cortical thickness (C.Th) of patients treated with definitive RT for oropharyngeal cancer using quantitative computed tomography (CT). Forty-four patients with squamous cell carcinoma of the oropharynx treated with definitive chemoradiotherapy between 2016-2017 were included in this Institutional Review Board-approved study. A validated bone mapping technique was used to examine the cortical bone changes in the mandible. Briefly, the mandible was segmented from baseline and follow-up clinical CT data using Mimics and C.Th was calculated using Stradwin at thousands of points across the mandibular surface. Iterative closed point (ICP) registration was performed in a computer algorithm software and cortical changes between baseline and follow-up were calculated for corresponding points. The significance of the changes for each point on the surface between the baseline and follow-up scans was calculated. Statistical analyses on the surface maps were performed using a computer software toolbox for the statistical analysis of univariate and multivariate data using linear mixed effects models. The majority of patients had stage III-IV disease (98%) and a tonsil or base of tongue primary (93%). The median age was 60 years and 91% were male. All patient received concurrent chemotherapy and 11% received additional induction chemotherapy. Dental extractions were performed prior to RT in 63%; 4 patients were edentulous. Median time between baseline and follow-up imaging was 90.5 days (range, 25-190). Median volumes receiving 60 Gy for the symphysis, body, angle, and ramus were 0.8%, 29%, 76%, and 43% respectively. Mean C.Th at baseline and follow-up were 2.6 mm (95% CI 2.5-2.7) and 2.4 mm (95% CI 2.3-2.5) respectively, with an overall mean difference of 0.2 mm (95% CI 0.1-0.2, p<0.001). Significant C.Th loss was observed bilaterally at all anatomic locations, however symphyseal and proximal regions (-8.9%) incurred the greatest loss across patients. Greater C.Th loss was observed in patients that underwent pre-RT dental extractions (-7.0%, p<0.001) than those that did not (-4.6%, p=0.11). This study provides new insights into the early effects of head and neck RT on the mandible and suggest an increased bone remodeling following treatment throughout the mandible. Dental extractions prior to RT increase the extent of bone loss. No dose response was observed in this study, however further evaluation of a dose-response relationship are warranted.

Skeletal Changes Associated with Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disorder in which progressive articular cartilage loss occurs alongside pathological changes in subchondral bone and other joint tissues. The pathophysiological role of bone in OA has been a point of interest for many years and has resurfaced again in recent years as a potential target for new treatments. Articular cartilage and subchondral bone together form the osteochondral unit. Its homeostasis and integrity are reliant on biochemical crosstalk and biomechanical interplay between the two. Subchondral bone, with its relatively greater stiffness and strength, provides mechanical support to the overlying cartilage and absorbs much of the mechanical force transmitted through the joint. Mechanical instability in osteoarthritic joints is thought to be a significant risk-factor in joint disease, due to the mechano-sensitive nature of many of its native tissues. Although the progression of joint disease remains incompletely understood, significant changes in subchondral bone remodelling, structure, composition, and mechanical properties have been documented in animal and human studies of OA. The purpose of this review is to explore and discuss these bony changes associated with disease and, in particular, contextualise the basic science and clinical literature on the role of subchondral bone in OA.

Bone Regeneration Effect of Hyperbaric Oxygen Therapy Duration on Calvarial Defects in Irradiated Rats.

Objective In this study, we evaluated changes in bone remodeling in an irradiated rat calvarial defect model according to duration of hyperbaric oxygen therapy. Materials and Methods The 28 rats were divided into four groups. Radiation of 12 Gy was applied to the skull, and 5-mm critical size defects were formed on both sides of the skull. Bone grafts were applied to one side of formed defects. From the day after surgery, HBO was applied for 0, 1, and 3 weeks. At 6 weeks after bone graft, experimental sites were removed and analyzed for radiography, histology, and histomorphometry. Results Micro-CT analysis showed a significant increase in new bone volume in the HBO-3 group, with or without bone graft. When bone grafting was performed, BV, BS, and BS/TV all significantly increased. Histomorphometric analysis showed significant increases in %NBA and %BVN in the HBO-1 and HBO-3 groups, regardless of bone graft. Conclusion Hyperbaric oxygen therapy was effective for bone regeneration with only 1 week of treatment.

The Role of Dickkopf-1 in Thyroid Hormone-Induced Changes of Bone Remodeling in Male Mice.

Thyroid hormones regulate bone homeostasis, and exogenously induced hyperthyroidism and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitor Dickkopf-1 (Dkk1), a determinant of bone mass. Here, we assessed the role of Dkk1 in thyroid hormone-induced changes in bone using conditional Dkk1 knockout mice. Male mice with a global (Dkk1fl/fl;Rosa26-CreERT2) or osteocyte-specific (Dkk1fl/fl;Dmp1:Cre) deletion of Dkk1 were pharmacologically rendered hypothyroid or hyperthyroid. The bone phenotype was analyzed using micro-CT analysis, dynamic histomorphometry, and serum concentrations of bone turnover markers. Hypothyroid and hyperthyroid Cre-negative mice of either Cre line revealed the expected changes in bone volume with hypothyroid mice displaying a 40% to 60% increase in vertebral trabecular bone volume, while hyperthyroid mice lost 45% to 60% of bone volume. Similar changes were observed at the spine. Interestingly, Cre-positive mice of both lines did not gain or lose as much bone at the femur when rendered hypothyroid or hyperthyroid. While Cre-negative hypothyroid mice gained 80% to 100% bone volume, Cre-positive hypothyroid mice only increased their bone volume by 55% to 90%. Similarly, Cre-negative hyperthyroid mice lost 74% to 79% bone, while Cre-positive hyperthyroid mice merely lost 40% to 54%. Despite these site-specific differences, both global and osteocyte-specific Dkk1 knockout mice displayed similar changes in bone turnover as their Cre-negative controls in the hypothyroid and hyperthyroid states. While osteoblast and osteoclast parameters were increased in hyperthyroidism, hypothyroidism potently suppressed bone cell activities. Loss of Dkk1 is not sufficient to fully reverse thyroid hormone-induced changes in bone mass and bone turnover.

The Impact of Roux-en-Y Gastric Bypass on Bone Remodeling Expressed by the P1NP/βCTX Ratio: a Single-Center Prospective Cohort Study.

Bariatric surgery seems to decrease bone mineral density and increase the risk of fatigue fractures. P1NP (bone formation) and βCTX (bone resorption) were recently validated as reference bone turnover markers (BTM). To assess changes in bone remodeling in severely obese patients undergoing Roux-en-Y gastric bypass (RYGB) by using a new composite biomarker, the P1NP/βCTX ratio. We prospectively collected blood samples preoperatively, at 1month and at 1year from 114 consecutive RYGB patients from 12/2012 to 04/2014. Repeated measures ANOVA and multiple regression were used for data analysis. Cumulative incidence of fractures was assessed in 06/2018. The P1NP/βCTX ratio decreased significantly (P < 0.001) from baseline to 1month and 1year (180 ± 6.6, 110 ± 4.1, and 132 ± 5.4). The 1-year P1NP/βCTX ratio did not correlate with BMI or ΔBMI, but inversely correlated with age (r = - 0.23, P = 0.014) and with hsCRP (r = - 0.26, P = 0.009), even after adjustment for age, sex, BMI, and lifestyle, and linearly correlated with albumin (r = 0.2, P = 0.037). At baseline, none of these correlations were detectable. Serum for all time-points was available from > 94% of the patients. At a median follow-up of 4.7years, 8 patients (7.3%) had a bone fracture, all of them traumatic. Following RYGB, bone remodeling increases, with a shift toward degradation. This effect seems to be weight-loss independent and shows a correlation with age,with the level of systemic inflammation, and with nutritional state. The risk of fractures should be assessed systematically in bariatric patients and measures of prevention should be improved accordingly.

Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol.

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.

Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model

Background ContextDiabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. ObjectiveThe aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. Study designStreptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. MethodsWe divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. ResultsIn the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05). ConclusionsEven if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.

Proximal Femoral Bone Regeneration After an Uncemented Hydroxyapatite-coated Long-stem in Revision Hip Surgery.

Background:Bone remodelling with lateral femoral cortex thinning is a major concern after extensively porous-coated long-stem in revision surgery. Extensive hydroxyapatite coated long-stems were introduced to improve osseointegration, but bone remodelling changes have not been quantified.Objective:The question of whether bone remodelling changes from extensive hydroxyapatite-coated long stems influence the durability of femoral revision, clinical outcome is assessed in follow-up radiographs.Methods:Uncemented straight monoblock hydroxyapatite-coated long-stems used in revision hip surgery for aseptic loosening were assessed in a consecutive series of 64 hips (60 patients). Mean follow-up was 8.6 years and the mean age at surgery was 70 years (27-91). The pre-operative bone defect was classified according to Paprosky. Cortical struts were not used in this series. Cortical index and femoral cortical width were measured at three different levels at different periods.Results:Four patients with pain under level 4 due to stem loosening needed an exchange surgery of their femoral component, but two patients rejected re-surgery. The cumulative probability of not having aseptic loosening was 91.2% (95% confidence interval 73.5-96.9) at 10 years according to Kaplan and Meier. Twenty-seven of 35 osteolytic lesions had disappeared or decreased at the last follow-up. The thickness of the lateral and medial cortex increased over the course of the study at different levels. Increases of femoral cortex thickness were greater in men and in cases with mild bone defects.Conclusion:Although clinical outcome of the hydroxyapatite-coated long stem in revision surgery is good but not outstanding, most osteolytic lesions heal and the femoral cortex thickness increases at different levels.

Two different cementless femoral components in primary total hip arthroplasty.

The results of first (51 Harris-Galante stems with an average follow-up of 12.3 years) and second generation (53 MultiLock stems with an average of 6.4 years) cementless femoral stems in total hip replacement were analysed. Ten Harris-Galante stems were revised (9.8% at 8 years and 22.8% at 13 years) and one unstable MultiLock stem (2.6% at 8 years). Thirty-seven Harris-Galante and 45 MultiLock stems were osseo-integrated. Femoral osteolysis was seen in 21 Harris-Galante (26.6% at 8 years and 43.7% at 13 years) and in 3 MultiLock stems (8.0% at 8 years). At intermediate follow-up, second generation stems show less bone remodelling changes than first generation stems at the same interval. Distal osteolysis and pronounced stress-shielding have not been encountered in second generation stems. (Hip International 2002; 12: 289-302).

Least-detectable and age-related local in vivo bone remodelling assessed by time-lapse HR-pQCT.

We previously developed an image analysis approach for the determination of local sites of bone remodelling using time-lapse in vivo HR-pQCT. The involved image filtering for removing noise was chosen rather aggressively, and also removed some effects of the bone remodelling. In this paper, we quantify these filtering settings using ex vivo reproducibility HR-pQCT images, and determine the least-detectable bone remodelling using in vivo reproducibility HR-pQCT images, as well as testing whether the approach is capable of capturing age-related bone remodelling by use of in vivo long-term HR-pQCT images. We found that a threshold value of 225 mg HA/cm3 for the filtering led to acceptable results with falsely determined bone remodelling of less than 0.5%, and that the least-detectable bone formation and bone resorption are 2.0 ± 1.0% and 2.2 ± 0.7% respectively. We also found that age-related local bone remodelling can be captured satisfactorily in postmenopausal women. The latter revealed new insights into the effect of ageing on bone remodelling, and showed that bone remodelling seems to take place through a few small formation packets and many large resorption volumes leading to a net bone loss. We conclude that local in vivo bone remodelling can be successfully assessed with time-lapse in vivo HR-pQCT capable of assessing age-related changes in bone remodelling.

Influence of collars on the primary stability of cementless femoral stems: A finite element study using a diverse patient cohort

For cementless femoral stems, there is debate as to whether a collar enhances primary stability and load transfer compared to collarless designs. Finite Element (FE) analysis has the potential to compare stem designs within the same cohort, allowing for subtle performance differences to be identified, if present. Subject-specific FE models of intact and implanted femora were run for a diverse cohort (21 males, 20 females; BMI 16.4-41.2 kg/m2 , age 50-80 yrs). Collared and collarless versions of Corail® (DePuy Synthes, Warsaw, IN) were sized and positioned using an automated algorithm that aligns the femoral/stem axes, preserves the head-center location, and maximizes metaphyseal fit. Joint contact and muscle forces simulating peak forces in level gait and stair climbing and were scaled to the body mass and applied to each subject. Three failure scenarios were assessed: Potential for peri-prosthetic fibrous tissue formation (stem micromotion), potential for peri-prosthetic bone damage (equivalent strains), and calcar bone remodeling (changes in strain-energy density). Comparisons were performed using paired t-tests. Only subtle differences were found (mean 90th percentile micromotion: Collared = 86 µm, collarless = 92.5 µm, mean 90th percentile interface strains: Collared = 733 µϵ, collarless = 767 µϵ, and similar remodeling stimuli were predicted). The slight differences observed were small in comparison with the inter-patient variability. Statement of clinical significance: Our results suggest that the presence/absence of a collar is unlikely to substantially alter the bone-implant biomechanics nor the initial mechanical environment. Hence, a collar is likely to have minimal clinical impact. Analysis using different femoral stem designs is recommended before generalising these findings. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1185-1195, 2018.

Two-dimensional and three-dimensional postsurgical temporomandibular joint condylar remodelling following vertical subsigmoid osteotomy setback surgery

Background: Vertical subsigmoid osteotomy (VSSO) for ramus setback has been suggested to exert less stress onto the condylar head causing more positive bone remodelling changes in the postoperative phase. However, it is unclear if the setback amount has any effect on the remodelling pattern. Objectives: This study aims to compare the postsurgical quantitative and qualitative condylar remodelling changes in various setback magnitudes using two-dimensional (2D) and threedimensional (3D) radiography. Methods: Retrospective pre- and postoperative radiographic data of patients with mandibular prognathism that had undergone VSSO from 2007 to 2012 at the Prince Philip Dental Hospital were traced. 130 postero-anterior and lateral cephalographs, along with 174 cone-beam computed tomography (CBCT) scans were retrieved. 2D and 3D radiographic tracing were performed to measure the condyle-ramal morphometric values. Pre- and postoperative CBCT rendered condyle ramus segments were superimposed based on stable growth registration points to observe zonal and topographic changes. Findings and Conclusion: 2D radiographic tracing did not show significant condyle-ramal changes in different setback magnitudes. 3D radiographic tracing showed significant changes in axial condylar depth with more setback. Topography analysis also showed that in the postero-superior condylar surface, more bone deposition was found in larger setback. In the axial plane, the bone formation proportion at the condylar head was significantly increased in mid-anterior and posteromedial zones with larger setback except in the group with setback between 4.1–6 mm. In general the condylar remodelling pattern after VSSO for mandibular setback was considered to be stable despite various setback magnitudes.

Bariatric Roux-En-Y Gastric Bypass Surgery: Adipocyte Proteins Involved in Increased Bone Remodeling in Humans.

Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB). Anthropometric data, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), collagen type 1 C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-VitD), leptin, adiponectin, RANKL, OPG, and sclerostin of 30 menstruating women were measured preoperatively (Pre), and 3, 12, and 24months (m) after RYGB. Leptin (34.4 (14.7; 51.9) vs. 22.5 (1.9; 52.7) ng/mL) and OPG (3.6 (1.1; 11.5) vs. 3.4 (1.5; 6) pmol/L) decreased, and adiponectin (7.4 (1.7; 18.4) vs. 13.8 (3.0; 34.6) μg/mL), CTX (0.2 (0.1; 2.2) vs. 0.6 (0.4; 6.0) ng/mL), RANKL (0.1 (0.0; 0.5) vs. 0.3 (0.0; 2.0) pmol/L), and sclerostin (21.7 (3.2; 75.1) vs. 34.8 (6.4; 80.5) pmol/L) increased after 3m. BSAP increased after 12m (10.1 (5.4; 18.9) vs. 13.9 (6.9; 30.2) μg/mL) (p<0.005). CTX correlated positively with adiponectin at 24m and inversely with leptin Pre; OPG at 3m; weight, FM, FFM, and leptin at 24m. RANKL correlated directly with weight at 3m. Sclerostin correlated inversely with weight Pre and FM at 3m. BSAP correlated negatively with 25-OH-VitD at 12m, and positively with PTH at 24m. RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.

Does Local Application of Strontium Increase Osteogenesis and Biomaterial Osteointegration in Osteoporotic and Other Bone Tissue Conditions: Review of Literature

Summary Osteoporosis and other pathological bone conditions can impair bone regeneration properties, consuming in increased morbidity and decreased quality of life. Changes of bone healing can result in poor osteointegration and surgical failures if implants are used. To overcome and facilitate bone regeneration, more attempts are made to develop an ideal synthetic scaffold with better biocompatibility, osteoconductivity, bioactivity, osteoinductivity and interconnected porosity. It is considered that strontium, being similar to calcium, can be incorporated into the mineral phase of the bone remodeling. This quality had led strontium to be used as an osteoporotic medication to improve quality of bone and to reduce the risk of bone fractures. Also local application of strontium has been widely used within different biomaterials in tissue engineering researches. In this review authors wanted to provide an overview about strontium, its mechanisms of action in bone tissue and initiated changes of bone remodeling within biomaterials.

The incorporation of fluoride and strontium in hydroxyapatite affects the composition, structure, and mechanical properties of human cortical bone.

Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naïve osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naïve osteoporotic bone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017.

Osteoporosis

IntroductionOsteoporosis is a complex disease whose aetiopathogenic mechanisms lead to a structural disorder or low bone mass as a result of changes in bone remodelling that increase bone fragilty. These changes can be caused by endocrine, metabolic and immunologic disorders, among others. Clinical manifestationsOsteoporosis is an asymptomatic disease, whose only clinical manifestation is its complication: osteoporotic fracture, the only cause of its morbidity and mortality. The most common fractures, occurring in the vertebrae, can go unnoticed. Hip and Colles’ fractures are almost always the result of a fall. In the absence of a fracture, clinical suspicion will be reached by assessing the risk factors. DiagnosisThe diagnosis of osteoporosis is based on the densitometric criteria of the World Health Organisation, which are based on the bone mineral density in the lumbar spine or proximal femur using dual energy X-ray absorptiometry. Once the diagnosis has been made, osteoporosis should be ruled out as secondary. TreatmentNew therapeutic strategies offer improved treatment of the disease.

Pore network microarchitecture influences human cortical bone elasticity during growth and aging

Cortical porosity is a major determinant of bone strength. Haversian and Volkmann׳s canals are׳seen’ as pores in 2D cross-section but fashion a dynamic network of interconnected channels in 3D, a quantifiable footprint of intracortical remodeling. Given the changes in bone remodeling across life, we hypothesized that the 3D microarchitecture of the cortical pore network influences its stiffness during growth and ageing.Cubes of cortical bone of 2 mm side-length were harvested in the distal 1/3 of the fibula in 13 growing children (mean age±SD: 13±4 yrs) and 16 adults (age: 75±13 yrs). The cubes were imaged using desktop micro-CT (8.14µm isotropic voxel size). Pores were segmented as a solid to assess pore volume fraction, number, diameter, separation, connectivity and structure model index. Elastic coefficients were derived from measurements of ultrasonic bulk compression and shear wave velocities and apparent mass density.The pore volume fraction did not significantly differ between children and adults but originates from different microarchitectural patterns. Compared to children, adults had 42% (p=0.033) higher pore number that were more connected (Connective Density: +205%, p=0.001) with a 18% (p=0.007) lower pore separation. After accounting for the contribution of pore volume fraction, axial elasticity in traction-compression mode was significantly correlated with better connectivity in growing children and with pore separation among adults.The changes in intracortical remodeling across life alter the distribution, size and connectedness of the channels from which cortical void fraction originates. These alterations in pore network microarchitecture participate in changes in compressive and shear mechanical behavior, partly in a porosity-independent manner. The assessment of pore volume fraction (i.e., porosity) provides only a limited understanding of the role of cortical void volume fraction in its mechanical properties.

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator (agr) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis.