Investigate Bone Loss Research Articles

Dental Implants in 18 Patients with Systemic Scleroderma: A Retrospective Radiographic Analysis Over a 5-Year Period with Focus on Marginal Bone Loss.

Patients with systemic scleroderma (SSc) often suffer from premature tooth loss. The aim of this study was to radiologically investigate bone loss at dental implants in patients with SSc and compare it with data from the literature on healthy patients. Mesial and distal bone level changes at implants were independently determined on panoramic and intraoral radiographs. They were double-checked after determination of evaluability by three different raters. Cohen's kappa was used to test for interrater reliability. Mean bone loss was estimated using linear regression analysis considering the patient as a random-effect implant and performed separately in predefined implant regions for different time points and for the mesial and distal sides of the implants. Mesial and distal bone level changes were analyzed in 61 implants using periapical and panoramic radiographs. In total, 114 radiographs from 18 patients were evaluable in both the mesial and distal regions. After a maximum observation period of 60 months, the mean peri-implant bone loss was 1.68 mm (range: 0.83 to 2.54 mm) at the distal aspect and 1.65 mm (range: 0.81 to 2.48 mm) at the mesial aspect in the right posterior mandible (region 44 to 47 [FDI numbering system]), whereas in the left posterior maxilla (regions 24 to 27), the mean peri-implant bone loss was 0.61 mm (range: 0.32 to 0.91 mm) at the distal aspect and 0.59 mm (range: 0.16 to 1.03 mm) at the mesial aspect. The mean bone loss 60 months after surgery was 1.05 mm (range: 0.85 to 1.25 mm). Marginal bone loss at implants in patients with SSc is comparable to data from the literature collected in healthy subjects.

Does glenoid bone loss accompany posterior shoulder instability with only labral tear? A magnetic resonance imaging-based study.

The primary aim of this study was to investigate bone loss in the glenoid with magnetic resonance imaging in posterior shoulder instability with only a labral tear. A total of 76 patients operated on because of posterior and anteroposterior shoulder instability only with a labral tear between 2006 and 2019 (n=40 and n=36, respectively) were included in this study. The instability type, a presence of an additional superior labrum anteroposterior (SLAP) lesion, the number of dislocations, and the magnetic resonance imaging-based measurements (the glenoid diameter and the bone defect size in the glenoid, the Hill-Sachs lesion [HSL] and the reverse HSL [rHSL] length, the angle and the arc length of HSL and rHSL, and the humerus head diameter and its area) were analyzed. The size of the anterior glenoid defect, the rHSL measurements (length, angle, and arc length), and the ratio of the anterior glenoid defect size to the glenoid diameter were significantly higher for anteroposterior instability (P<.01) cases. There was no significant difference (P=.49, .64, and .82, respectively) for the presence of an additional SLAP pathology, the glenoid diameter, the posterior glenoid defect, and the ratio of the posterior glenoid defect size to the glenoid diameter in posterior and anteroposterior instability groups. The increased number of dislocations was associated with increased rHSL length and total arc length (P=.04 and .03, respectively). An additional SLAP lesion in posterior shoulder instabilities was not associated with the bone defect size (P=.29). Although the posterior shoulder instability with only a labral tear is likely to cause a bone defect, we have shown that the instability is not expected to be caused by the bone defect. Therefore, this study points out that only soft tissue repair without considering the bone defect could be promising in this patient group.

Micro-CT Study of Mongolian Gerbil Humeral Bone After Prolonged Spaceflight Based on a New Algorithm for Delimitation of Long-Bone Regions.

The Mongolian gerbil displays unique physiological and anatomical features that make this species an attractive object for biological experiments in space. However, until recently, the Mongolian gerbil has remained a novel, mostly unstudied animal model in investigating bone loss in weightlessness (G0). After 12 days of orbital Foton-M3 mission, the humerus of Mongolian gerbils has been studied here via micro-computed tomography (micro-CT) to quantify bone morphometric parameters. The samples from the flight group, delayed synchronous ground-control group, and basal control group were investigated, and main morphometric parameters were reported in the article. The accurate selection of a region of interest is an essential step for a correct assessment of bone parameters. We proposed a new, easy and efficient method for delimiting the bone’s basic regions in the humerus. It is based on quantitative estimation of X-ray attenuation in the cortical bone as a function of humerus bone length. The micro-CT analysis of the basic bone regions revealed a difference in bone morphometric parameters between the flight and control gerbils. The most significant bone loss was observed in the cortical part of the proximal humeral zone in the flight group. No statistically significant changes of volume fraction in the cancellous tissue of proximal and distal epiphyses and metaphyses were observed. A statistically significant increase in both cancellous bone volume and bone X-ray attenuation in the flight group was detected in the proximal part of the diaphyses. We assume that enhanced calcium deposition in the diaphyseal cancellous tissue occurred due to a bone response to G0 conditions.

Identification of non-Hodgkin lymphoma patients at risk for treatment-related vertebral density loss and fractures

SummaryInformation on bone loss in treated non-Hodgkin’s lymphoma patients is limited. In this study, we used CT to analyze bone loss as well as prevalent and incident fractures. We found severe bone loss, a high rate of fractures, and a novel association between bone loss and the international prognostic index.IntroductionTo investigate bone loss and fracture risk in non-Hodgkin-lymphoma (NHL) patients by (i) comparing treatment-related vertebral density (VD) loss in NHL patients with control subjects and (ii) investigating associations of VD loss versus fracture risk. Further, associations of VD loss and clinical parameters were investigated.MethodsVD of 123 NHL patients was measured pre- and post-treatment in the L1, L2, and L3 vertebrae in routine computed tomography (CT) scans, performed between Jan 2016 and Mar 2017. Control measurements (n = 52) were obtained from CT colonographies between Sept 2003 and Sept 2017 and their subsequent follow-up-exams (10–137 months).Prevalent and incident (between baseline and follow-up) fractures were assessed in all subjects, and VD loss per year was calculated. Linear regression models were used to (i) compare VD loss between patients and controls and (ii) identify associations between VD loss and clinical parameters. Using logistic regression models, ORs for fractures per SD change in VD were assessed in patients. Analyses were adjusted for age, sex, and contrast application.ResultsNHL patients experienced significantly greater VDL1–3 loss than controls (P = 0.003), and greater VDL1–3 loss was associated with a greater likelihood of incident fractures (OR, [95%-CI], P 1.90, [1.03, 3.51], 0.04). Patients with an initial international prognostic index (IPI) of 5 suffered significantly greater VD loss compared with an IPI of 0 (P = 0.01).ConclusionUsing VD measurements in routine CT scans, substantial vertebral bone loss in NHL patients could be documented with a high incidence of fractures.

Bone loss in the anterior edentulous maxilla opposing two-implant-supported overdentures vs complete dentures: a systematic review and meta-analysis

To investigate bone loss in the anterior edentulous maxilla restored with maxillary complete dentures and opposed by mandibular two-implant-supported overdentures (2-IODs) or complete dentures. A systematic search was conducted using the Ovid MEDLINE, Embase, Web of Science, CINAHL, and Cochrane databases for studies investigating bone loss in the anterior edentulous maxilla with mandibular 2-IODs or complete dentures. Two reviewers assessed the eligibility of studies and risk of bias assessment was conducted according to the Newcastle-Ottawa Scale. A meta-analysis was performed using statistical software to estimate weighted mean difference in bone loss with 95% confidence interval (CI). The level of significance was defined as P value (< .05). A total of 2,510 studies were identified through electronic and manual searching. Six studies were selected and compounded for quantitative synthesis of 163 patients. Bone loss in the anterior edentulous maxilla was greater with 2-IODs than with complete dentures. The total estimate of weighted mean difference between 2-IODs and complete dentures was -1.40 (95% CI -3.12 to 0.31). However, the difference was not statistically significant (P = .11). The data were heterogenous across the studies based on chi-square statistics (χ2 [df = 7] = 52.75, P < .0001; τ2 = 5.53, I2 = 95.21%). In addition, the impact of implant splinting on bone loss was not significant (P > .29). None of the included studies were considered to be at high risk of bias. Within the limitations of the current systematic review and meta-analysis, the estimate of bone loss in the anterior edentulous maxilla was greater with 2-IODs than with complete dentures. However, the difference was not statistically significant. A well-designed randomized clinical study needs to be conducted to validate the results of this systematic review.

Effect of ovariectomy on proximal tibia metaphysis and lumbar vertebral body in common marmoset monkeys.

This study aimed to investigate the effect of estrogen withdrawal on bone tissue in adult female marmoset monkeys. In a 1-year follow-up study we used quantitative computer tomography to measure total bone mineral density (BMD) of the proximal tibia and the second-last lumbar vertebral body (L5/L6) before and 1, 3, 6, and 12 months after ovariectomy. Body mass did not significantly change during the 1-year observation period. However, a significant decline of total BMD after ovariectomy was observed in the proximal tibia but not in L5/L6. In addition, regression analysis showed a significant positive relationship between BMD and body mass in both tibia and L5/L6. The results of our study support the idea that ovariectomized marmoset monkeys may serve as a model to investigate bone loss related to decline of estrogen production.

Psychosocial stress and bone loss among postmenopausal women: results from the Women’s Health Initiative

BackgroundBone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few...

MiR-181c-5p mediates simulated microgravity-induced impaired osteoblast proliferation by promoting cell cycle arrested in the G2 phase.

Impaired osteoblast proliferation plays fundamental roles in microgravity‐induced bone loss, and cell cycle imbalance may result in abnormal osteoblast proliferation. However, whether microgravity exerts an influence on the cell cycle in osteoblasts or what mechanisms may underlie such an effect remains to be fully elucidated. Herein, we confirmed that simulated microgravity inhibits osteoblast proliferation. Then, we investigated the effect of mechanical unloading on the osteoblast cell cycle and found that simulated microgravity arrested the osteoblast cell cycle in the G2 phase. In addition, our data showed that cell cycle arrest in osteoblasts from simulated microgravity was mainly because of decreased cyclin B1 expression. Furthermore, miR‐181c‐5p directly inhibited cyclin B1 protein translation by binding to a target site in the 3′UTR. Lastly, we demonstrated that inhibition of miR‐181c‐5p partially counteracted cell cycle arrest and decreased the osteoblast proliferation induced by simulated microgravity. In conclusion, our study demonstrates that simulated microgravity inhibits cell proliferation and induces cell cycle arrest in the G2 phase in primary mouse osteoblasts partially through the miR‐181c‐5p/cyclin B1 pathway. This work may provide a novel mechanism of microgravity‐induced detrimental effects on osteoblasts and offer a new avenue to further investigate bone loss induced by mechanical unloading.

Simulated microgravity reduces intracellular-free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts.

Calcium homeostasis in osteoblasts plays fundamental roles in the physiology and pathology of bone tissue. Various types of mechanical stimuli promote osteogenesis and increase bone formation elicit increases in intracellular-free calcium concentration in osteoblasts. However, whether microgravity, a condition of mechanical unloading, exerts an influence on intracellular-free calcium concentration in osteoblasts or what mechanisms may underlie such an effect are unclear. Herein, we show that simulated microgravity reduces intracellular-free calcium concentration in primary mouse osteoblasts. In addition, simulated microgravity substantially suppresses the activities of L-type voltage-sensitive calcium channels, which selectively allow calcium to cross the plasma membrane from the extracellular space. Moreover, the functional expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors, which mediate the release of calcium from intracellular storage, decreased under simulated microgravity conditions. These results suggest that simulated microgravity substantially reduces intracellular-free calcium concentration through inhibition of calcium channels in primary mouse osteoblasts. Our study may provide a novel mechanism for microgravity-induced detrimental effects in osteoblasts, offering a new avenue to further investigate bone loss induced by mechanical unloading.

Peri-implant Bone Loss of Tissue-Level and Bone-Level Implants in the Esthetic Zone with Gingival Biotype Analysis.

The esthetic outcome of dental implants can be compromised when some degree of bone loss occurs around the implant. This may particularly affect the tissue-level (TL) design. Therefore, bone-level (BL) design implants may be preferable if a natural emergence profile is important. Notwithstanding the implant design, the gingival biotype has been identified as a crucial factor in the stability of crestal bone. The objective of this study was to investigate bone loss in patients with different gingival biotypes at TL and BL implant sites in the esthetic zone. In 41 patients, 20 TL and 22 BL implant procedures were carried out. Intraoral radiographs of all of the 42 sites were taken immediately after implant insertion as well as during the follow-up examination. The analysis of bone height was conducted using a computerized technique. The TRAN method was used to determine the gingival biotype. After a mean in situ period of 4.9 years in the TL group, 12 implants with a thick biotype had a mean bone loss of 0.21 mm (SD: 0.43 mm). The eight implants with a thin biotype had a loss of 0.05 mm (SD: 0.47 mm; P = .31). After a mean in situ period of 1.9 years, the 14 BL sites with a thick biotype showed a mean bone change of -0.03 mm (SD: 0.38 mm). In the eight implants with a thin biotype, a change of +0.09 mm (SD: 0.32 mm; P = .84) was noted. Analysis of the obtained results did not reveal a dependency of bone height on implant design or on gingival biotype. However, prior to choosing an implant design, it may nevertheless be beneficial to screen for transparent soft tissues, where the BL design offers a more natural emergence profile. For this purpose, the TRAN method is clearly the fastest and easiest.

Abstract P6-08-12: Understanding the etiology of osteopenia and osteoporosis in young breast cancer survivors compared to cancer-free women

Abstract Background: Our group previously reported that young breast cancer (BC) survivors have a higher risk of osteopenia/osteoporosis compared to their cancer-free peers. In order to develop successful interventions we need to understand the major contributing factors. Therefore, we investigated bone loss in young BC survivors by age at diagnosis, tumor characteristics and BC treatment compared to their cancer-free peers. Methods: We studied 775 women (211 BC survivors, 564 cancer-free) with familial risk of breast and/or ovarian cancer in the Breast and Ovarian Surveillance Service (BOSS) cohort at Johns Hopkins. Survivors were diagnosed with stage 0-III BC &amp;lt;5 years prior to enrollment. The comparison group was cancer-free women at enrollment. Osteopenia and osteoporosis were ascertained based on self-reported physician diagnosis in baseline and follow-up questionnaires. Prevalent cases of osteopenia or osteoporosis were excluded. Multivariable (MV)-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of osteopenia and/or osteoporosis among BC survivors compared to cancer-free women. BC survivors were stratified by age at diagnosis, estrogen-receptor (ER) tumor status, and BC treatment. MV models were adjusted for age, menopausal status, body mass index, physical activity, smoking, alcohol use, hormone replacement therapy and early oophorectomy. Results: Mean time from BC diagnosis to enrollment was 1.4 years for survivors and mean age at BC diagnosis was 47 years. At baseline, BC survivors were more likely to be slightly older, postmenopausal, and current vitamin D users and less likely to have had an early bilateral oophorectomy compared to cancer-free women. During a mean follow-up time of 5.7 years, 66% of BC survivors and 54% of cancer-free women reported having ≥1 bone density exam and 112 incident cases of osteopenia/osteoporosis were identified (75% osteopenia only). BC survivors diagnosed at age ≤50 years had a 2-fold increased risk of osteopenia/osteoporosis compared to cancer-free women (HR=2.05, 95% CI=1.24-3.40). Risk of bone loss was similar among survivors with ER-positive tumors compared to cancer-free women (HR=2.04, 95% CI=1.30-3.22). No association was observed for BC survivors treated with tamoxifen only or chemotherapy only. BC survivors treated with aromatase inhibitors (AIs) only had almost 3-fold increased risk of osteopenia/osteoporosis compared to cancer-free women (HR=2.92, 95% CI=1.38-6.17). BC survivors treated with chemotherapy + tamoxifen and chemotherapy + AIs had over 2- and 4-fold increased risk of osteopenia/osteoporosis compared to cancer-free women (HR=2.28, 95% CI=1.04-5.00; HR=4.09, 95% CI=1.99-8.42, respectively). Results suggest that risk of bone loss was highest within 5 years after BC diagnosis. Conclusion: Our results demonstrate that osteopenia/osteoporosis incidence is higher in BC survivors compared to cancer-free women and risk varies by age at diagnosis, ER-status and BC treatment. Our findings provide support for a baseline evaluation of bone density close to diagnosis in BC survivors with familial risk. Future studies are needed to address the frequency of monitoring among specific age and treatment groups. Citation Format: Ramin CA, May BJ, Roden RBS, McCullough M, Armstrong DK, Visvanathan K. Understanding the etiology of osteopenia and osteoporosis in young breast cancer survivors compared to cancer-free women [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-12.

Hyperemesis gravidarum is not a negative contributing factor for postpartum bone mineral density

BackgroundHyperemesis gravidarum (HG), related to protracted vomiting and nausea, is a common cause of hospitalization during the first trimester of pregnancy. It can be accompanied by ketonuria, dehydration, and weight loss. Our aim was to investigate bone loss in patients with HG. MethodsIn our study, we investigated decreased bone mineral density (BMD)in a total of 79 patients (40 HG and 39 control) by means of dual energy X-ray absorptiometry (DEXA) measurements and laboratory parameters related to HG. All patients received DEXA measurement during the early postpartum period (usually two days after delivery, prior to discharge).This study was registered in the database via the Protocol Registration and Results System (PRS) (NCT03127293). ResultsThere was no significant difference in DEXA results (lumbar spine and total hip) and laboratory parameters between case and control groups, although a significant difference in vitamin intake was identified between cases and controls (65% vs. 92%, respectively, p = 0.003). Except for low serum levels of vitamin D, other laboratory parameters were in normal range in both groups. ConclusionPregnancies complicated by HG did not have decreased bone mineral density compared to those without HG. There is no evidence to relate HG to future osteoporosis.

Effects of local and systemic Atorvastatin on inflammation and alveolar bone loss in experimental periodontitis in rats

Background The first cause of tooth loss in developed countries is periodontitis and mostly occurs in people over 40 years old.Atorvastatin is a statin drug class, which has a revolutionary impact on the treatment of high cholesterol and also stimulates bone morphogenic protein which has osteogenic potential. The aim of this study was to evaluate the effect of local and systemic Atorvastatin in the treatment of periodontitis.Materials and Methods Forty eight Sprague Dawley rats were randomly divided into six groups of eight in each; experimental periodontitis was induced by ligature in five of them in each group daily (1) systemic Atorvastatin 12.5 mg/kg (2) systemic solvent (3) local Atorvastatin 0.25 mg/kg (4) local solvent (5) no drug was administered and group (6) left non-ligated, and rats were sacrificed on 11th day.Histopathological analysis on periodontal tissue; malondialdehyde (MDA) and superoxide dismutase (SOD) tests on serum were performed to investigate bone loss and inflammation. The statistical tests for MDA and SOD samples were one-way ANOVA with Duncan post-hoc whereas in histopathological samples nonparametric Kruskal–Wallis and Mann–Whitney tests were used.Results Although local injection and oral administration of Atorvastatin significantly decreased alveolar bone loss and serum MDA levels, no significant difference in their effectiveness was observed. Serum SOD levels were not significantly changed in all administered groups. P-value < 0.05.Conclusion In this study, both local injection and oral forms of Atorvastatin decreased inflammation and bone loss in periodontitis. However, no significant difference in their effectiveness was detected. However, local injection is superior to oral form due to effective lower dose.

The Factors Affecting Bone Density in Cirrhosis

Background:Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients.Objectives:We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it.Patients and Methods:In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant.Results:A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower vitamin D, higher Child score, and less GFRc.Conclusions:Abnormal DEXA was highly prevalent among patients with cirrhosis. The risk of this finding was increased by lower vitamin D levels, advanced disease, and impaired renal function.

Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™.

Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Unwrapping microcomputed tomographic images for measuring cortical osteolytic lesions in the 5T2 murine model of myeloma treated by bisphosphonate

Multiple myeloma is due to the proliferation of malignant plasma cells which increase the number of osteoclasts leading to trabecular and cortical bone osteolysis. The 5T2MM murine model reproduces the human disease and microcomputed tomography is a precise tool to investigate bone loss. Bisphosphonates (zoledronic acid or pamidronate) are used in preventing osteolysis. However, loss of cortical bone in not possible to quantify by histomorphometry on histological sections or microCT images.Osteolysis was studied in mice grafted with the 5THL subline to see if one drug was more active after 10 weeks. Mice were distributed into 4 groups: control, untreated, treated with pamidronate or with zoledronic acid. The left femurs were embedded undecalcified and sectioned at 7μm. The right tibias and femurs were analyzed by microCT and trabecular morphometric parameters were obtained. Cortical bone osteolysis was analyzed by developing a new algorithm to unwrap microCT sections of the cortices, allowing measurement of the number of perforations, porosity and mean perforation area.The bisphosphonates had no significant effect on the tumor growth as evidence by the absence of effect on the M-protein level. Cortical perforations were evidenced on histological sections and their number seemed to be reduced by both bisphosphonates. MicroCT was used to quantify the trabecular bone: a bone loss was evidenced in the untreated myeloma group and both bisphosphonates appeared equal to preserve trabecular mass. However, the number and size of cortical perforations cannot be determined on 3D models. Unwrapping microCT images provided flat images allowing a precise determination of cortical perforations. Pamidronate did not reduce the number and size of cortical perforations but significantly reduced porosity. Zoledronic acid appeared significantly superior and considerably reduced all parameters.Unwrapping microCT image is a new method allowing the measurement of cortical perforations in bone malignancies, a parameter that cannot be measured correctly on 2D histological sections.

Long-term persistence and switching patterns among women using osteoporosis therapies: 24- and 36-month results from POSSIBLE US™.

Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12months. Of 3,011 postmenopausal women treated in primary care, 36.8% continued baseline PMO medication during 36months of follow-up. Many factors were associated with nonpersistence, including newly initiating or switching therapy, and reporting moderate to severe side effects. Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12months. We describe 24- and 36-month persistence using patient-reported data from women with different PMO treatment histories in the US primary care setting. Data from 3,011 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™, 10/2005-12/2008) and Kaplan-Meier methods were used to estimate the probability of persisting (i.e., not discontinuing or switching PMO agents) with baseline PMO medication and hazard ratios for predictors of nonpersistence 24 and 36months after study entry. The probability of persisting with the baseline medication was 46.2% (95% confidence interval [CI] 44.2-48.1%) during 24months of follow-up and 36.8% (95% CI 34.7-38.9%) during 36months of follow-up. In adjusted analyses, newly initiating therapy or switching to a new agent, reporting moderate to severe side effects, having lower disease-specific quality of life scores, smoking, and residing in the South or West USA (all measured at study entry) were independent predictors of nonpersistence in both time periods. The majority of participants who discontinued therapy and had the opportunity to reinitiate (i.e., discontinued ≥4months before the end of follow-up) restarted therapy (24months 69%; 36months 75%). In this primary care cohort, a minority of women continued their baseline PMO therapy during a 24- to 36-month follow-up. Supporting patients during the initiation of a new therapy or if side effects occur may improve persistence and increase the therapeutic benefit of PMO medications.

Fear of falling, fracture history, and comorbidities are associated with health-related quality of life among European and US women with osteoporosis in a large international study

We studied 7,897 women with postmenopausal osteoporosis to assess factors that influence health-related quality of life (HRQoL). An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL. Understanding the factors that affect HRQoL may improve management of these patients. HRQoL is impaired in women treated for postmenopausal osteoporosis (PMO). The objective of this study was to examine the relationship between clinical characteristics, comorbidities, medical history, patient demographics, and HRQoL in women with PMO. Baseline data were obtained and combined from two large and similar multinational observational studies: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) and in the US (POSSIBLE US™) including postmenopausal women in primary care settings initiating or switching bone loss treatment, or who had been on bone loss treatment for some time. HRQoL measured by health utility scores (EQ-5D™) were available for 7,897 women (94% of study participants). The relationship between HRQoL and baseline clinical characteristics, medical history and patient demographics was assessed using parsimonious, multivariable, mixed-model analyses. Median health utility score was 0.80 (interquartile range 0.69-1.00). In multivariable analyses, young age, low body mass index, previous vertebral fracture, increased number of comorbidities, high fear of falling, and depression were associated with reduced HRQoL. Regression-based model estimates showed that previous vertebral fracture was associated with lower health utility scores by 0.08 (10.3%) and demonstrated the impact of multiple comorbidities and of fear of falling on HRQoL. In this large observational study of women with PMO, there was substantial interindividual variability in HRQoL. An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL.

Prevalence of Fracture Risk Factors in Postmenopausal Women Enrolled in the POSSIBLE US Treatment Cohort

Subject- and physician-reported data from 4,429 postmenopausal women receiving osteoporosis treatment in the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US) were used to assess the prevalence of risk factors (RFs) and on-study fracture. RFs assessed at study entry were age >70 years; fracture since age 50; minimum T-score (hip/spine) ≤−2.5 at diagnosis; body mass index <18.5 kg/m2; rheumatoid arthritis; parental history of hip fracture; current smoking; and recent oral glucocorticoid use. Data were collected with semiannual self-administered questionnaires. Results were stratified by physician-reported osteoporosis/osteopenia diagnosis. Low T-score and age >70 years were the most common RFs in the osteoporosis group, and age >70 years and prior fracture were the most common risk factors in the osteopenia group. Multiple RFs were more common than a single RF in osteoporotic women (54.2% versus 34.6%; P < 0.0001) but not osteopenic women (13.8% versus 33.6%; P < 0.0001). Women with multiple RFs had more on-study osteoporosis-related fractures than women with a single RF (osteoporosis group: 9.9% versus 6.2%; P = 0.0092; osteopenia group: 11.2% versus 4.7%; P < 0.0001). In postmenopausal women receiving osteoporosis treatment, multiple RFs increased fracture risk. RFs, in addition to bone mineral density, can help identify candidates for osteoporosis treatment.

Impact of Medication Adherence on Health Care Utilization and Productivity: Self-Reported Data From a Cohort of Postmenopausal Women on Osteoporosis Therapy

Background Many pharmacologic agents are approved for the prevention and treatment of osteoporosis, which is common among postmenopausal women. Evidence exists relating treatment persistence to fracture risk. Less is known about treatment persistence and the use of health care service and individual productivity. Objective This study was undertaken to describe health care use and productivity loss relative to osteoporosis medication persistence using women's self-reported data from the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™), a large, longitudinal (October 2004–December 2009) osteoporosis cohort study of postmenopausal women. Methods Analyses included women on pharmacologic osteoporosis therapy (alendronate, risedronate, ibandronate, calcitonin, raloxifene, or teriparatide) who provided health care use/productivity data collected using semiannual questionnaires over 1 year of follow-up. Participant characteristics, use, and productivity metrics were summarized. Logistic regression models and generalized linear models were used to examine use, time missed from usual activities, number of days spent in bed, and lost work time relative to treatment persistence, adjusting for potential confounders. Results At entry, of the 2528 women studied (91% white, 3.1% Hispanic/Latino, 2.3% African American/black, 1.1% Asian, and 2.1% American Indian/Native Alaskan, Native Hawaiian/Pacific Islander, or other; mean age, 64.6 [range, 37–97] years), 43.1% had osteoporosis and 23.4% had a previous fracture. After adjustment, subjects who switched therapies during follow-up were more likely to have had any kind of diagnostic testing (95.2% of switchers vs 91.2% of persistent subjects and 88.9% of discontinuers, P < 0.05). Discontinuers were less likely than persistent subjects to visit their primary care physicians (92.0% vs 94.4%, P = 0.0337). Variations in the number of days spent in bed, time missed from usual activities, and work loss (n = 852 employed subjects) by treatment persistence were not significant. Conclusions Use of diagnostic testing differed significantly by osteoporosis treatment status. Compared with women who persisted with treatment, primary care provider visits were less common among those who discontinued treatment. Treatment persistence was not associated with significant differences in productivity measures.