Understanding Osteoporosis: Pathophysiology, Risk Factors, Diagnosis, and Management

Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and deterioration of bone architecture, resulting in reduced bone strength and, consequently, increased susceptibility to fractures which poses a significant public health concern worldwide, particularly in aging populations [1]. The health-economic impact of vertebral and hip fractures has been extensively explored and it is well known that these fractures are associated with morbidity/disability and increased mortality;they also account for a substantial portion of the direct fracture costs. This review aims to provide a comprehensive overview of osteoporosis, including its pathophysiology, risk factors, diagnostic approaches, and management strategies. By elucidating the multifaceted nature of this condition, healthcare providers can better identify individuals at risk, implement preventive measures, and optimize treatment to reduce the burden of osteoporotic fractures.

Development and validation of a predictive model for spinal fracture risk in osteoporosis patients

BACKGROUND Spinal osteoporosis is a prevalent health condition characterized by the thinning of bone tissues in the spine,increasing the risk of fractures.Given its high incidence,especially among older populations,it is critical to have accurate and effective predictive models for fracture risk.Traditionally,clinicians have relied on a combination of factors such as demographics,clinical attributes,and radiological characteristics to predict fracture risk in these patients.However,these models often lack precision and fail to include all potential risk factors.There is a need for a more comprehensive,statistically robust prediction model that can better identify high-risk individuals for early intervention.AIM To construct and validate a model for forecasting fracture risk in patients with spinal osteoporosis.METHODS The medical records of 80 patients with spinal osteoporosis who were diagnosed and treated between 2019 and 2022 were retrospectively examined.The patients were selected according to strict criteria and categorized into two groups:Those with fractures(n=40)and those without fractures(n=40).Demographics,clinical attributes,biochemical indicators,bone mineral density(BMD),and radiological characteristics were collected and compared.A logistic regression analysis was employed to create an osteoporotic fracture risk-prediction model.The area under the receiver operating characteristic curve(AUROC)was used to evaluate the model’s performance.RESULTS Factors significantly associated with fracture risk included age,sex,body mass index(BMI),smoking history,BMD,vertebral trabecular alterations,and prior vertebral fractures.The final risk-prediction model was developed using the formula:(logit[P]=-3.75+0.04×age-1.15×sex+0.02×BMI+0.83×smoking history+2.25×BMD-1.12×vertebral trabecular alterations+1.83×previous vertebral fractures).The AUROC of the model was 0.93(95%CI:0.88-0.96,P<0.001),indicating strong discriminatory capabilities.CONCLUSION The fracture risk-prediction model,utilizing accessible clinical,biochemical,and radiological information,offered a precise tool for the evaluation of fracture risk in patients with spinal osteoporosis.The model has potential in the identification of high-risk individuals for early intervention and the guidance of appropriate preventive actions to reduce the impact of osteoporosis-related fractures.

Critical review of bone health,fracture risk and management of bone fragility in diabetes mellitus

The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes.Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk.Moreover,some antidiabetic medications further enhance the fragility of the bone.On the other hand,antiosteoporosis medications can affect the glucose homeostasis in these patients.It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk.Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature.With the advancement in imaging technology,newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes.The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients.Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Hip Fracture Risk Assessment Based on Different Failure Criteria Using QCT-Based Finite Element Modeling

Precise evaluation of hip fracture risk leads to reduce hip fracture occurrence in individuals and assist to check the effect of a treatment.A subject-specific QCT-based finite element model is introduced to evaluate hip fracture risk using the strain energy,von-Mises stress,and von-Mises strain criteria during the single-leg stance and the sideways fall configurations.Choosing a proper failure criterion in hip fracture risk assessment is very important.The aim of this study is to define hip fracture risk index using the strain energy,von Mises stress,and von Mises strain criteria and compare the calculated fracture risk indices using these criteria at the critical regions of the femur.It is found that based on these criteria,the hip fracture risk at the femoral neck and the intertrochanteric region is higher than other parts of the femur,probably due to the larger amount of cancellous bone in these regions.The study results also show that the strain energy criterion gives more reasonable assessment of hip fracture risk based on the bone failure mechanism and the von-Mises strain criterion is more conservative than two other criteria and leads to higher estimate of hip fracture risk indices.

Risk of fracture in celiac disease:Gender,dietary compliance,or both?

AIM:To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture risk.METHODS:We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age-and sex-matched controls who had been diagnosed with functional gastrointestinal disorders.Data were collected through in-person interviews with an investigator.The overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis).RESULTS:Compared with the control group,the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR):1.78,95% CI:1.23-2.56,P < 0.002] and in men (HR:2.67,95% CI:1.37-5.22,P < 0.004).Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003).In the time period after diagnosis,the risk of fractures was comparable between the CD cohort and controls in both sexes (HR:1.08,95% CI:0.55-2.10 for women;HR:1.57,95% CI:0.57-4.26 for men).CONCLUSION:CD patients have higher prevalence of fractures in the peripheral skeleton before diagnosis.This is associated with male sex and classic clinical presentation.The fracture risk was reduced after the treatment.

Fracture Risks Related to Parity and Breastfeeding Effect in Post-Menopausal Women Aged Sixty and Over: Results from the “Quality of Bone in Lorraine” Register

Introduction: The long term effect of accumulation of genital events as repeated pregnancy and longer breastfeeding in bone heath later in women’s life is still disputed. The objective was to assess the impact of parity and cumulated duration of breastfeeding on fracture risk in post-menopausal women aged sixty an over. Patients and Methods: It was a leading study from the register “Quality of Bone in Lorraine (QBL)” achieved in the department of endocrinology and osteoporotic disease of Nancy (France). This register included all patients sent for an assessment of the bone mass density from January 1, 2006 to December 31, 2014 (9 years). It was about post-menopausal women aged sixty an over suffering or not from osteoporosis fracture or bone fragility just after the age of 45. The genital events of patients to their age (from puberty to menopause) as well as the existence of hormone replacement therapy use, parity, and breastfeeding duration were taken into account. The assessment of bone fracture was clinical, radiological or by using the vertebral fracture assessment method. Results: 861 post-menopausal women were included. In comparison to the control group, the fractured population had a mean age of (74.3 ± 9 vs. 72 ± 8 years), a family history of fracture (32.1% vs. 26%), and an average input of calcium (2.4 ± 1 vs. 2.3 ± 0 portions per day). The age at menarche was of 12.8 ± 1 years in each group, a mean genital activity duration of (36.8 ± 3 vs. 37.2 ± 3 years), a parity of (2.1 ± 1 vs. 1.8 ± 1 children), a cumulated breastfeeding duration (4.2 ± 16 vs. 3.1 ± 5 months) and an age of menopause of (48.6 ± 4 vs. 48.6 ± 4 years) were respectively found in fractured and witness population. Overall, an osteoporotic fracture has been rediscovered in 50.9%. In multivariate analysis, only a cumulative duration of breastfeeding of 6 months and over was associated with a higher fracture risk (OR = 1.5 [1.1 - 2.2]). The impact of parity was not significant (OR = 1.1 [0.7 - 1.8]). Association with obesity was quasi significant (OR = 1.3 [0.9 - 1.9]). There was no correlation between the fracture risk and the genital activity duration (OR = 0.7 [0.5 - 1.0]), hormone replacement therapy use (OR = 1.0 [0.8 - 1.4]), daily calcium input (OR = 0.8 [0.6 - 1.3]), and age of menarche (OR = 1.0 [0.9 - 1.1]). Conclusion: This work confirms a negative impact from 6 months of cumulative breastfeeding. The modest effects observed may be related to the selection of Caucasian patients who live in an economically developed country with a limited number of pregnancies and limited duration of breastfeeding.

Parametric Study of Hip Fracture Risk Using QCT-Based Finite Element Analysis

Various parameters such as age,height,weight,and body mass index(BMI)influence the hip fracture risk in the elderly which is the most common injury during the sideways fall.This paper presents a parametric study of hip fracture risk based on the gender,age,height,weight,and BMI of subjects using the subject-specific QCT-based finite element modelling and simulation of single-leg stance and sideways fall loadings.Hip fracture risk is estimated using the strain energy failure criterion as a combination of bone stresses and strains leading to more accurate and reasonable results based on the bone failure mechanism.Understanding the effects of various parameters on hip fracture risk can help to prescribe more accurate preventive and treatment plans for a community based on the gender,age,height,weight,and BMI of the population.Results of this study show an increase in hip fracture risk with the increase of age,body height,weight,and BMI in both women and men under the single-leg stance and the sideways fall configurations.

Bone loss in chronic liver diseases:Could healthy liver be a requirement for good bone health?

Given that the liver is involved in many metabolic mechanisms,it is not surprising that chronic liver disease(CLD)could have numerous complications.Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients.Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis.Recent publications indicated that CLD-induced bone fragility depends on the etiology,duration,and stage of liver disease.Therefore,the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention,diagnosis,and treatment measures.The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood,especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals.It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals.Bone mineral density is widely used as the“golden standard”in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk.Therefore,microscale bone alterations(bone microstructure,mechanical properties,and cellular indices)were analyzed in CLD individuals.These studies further support the thesis that bone strength could be compromised in CLD individuals,implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients.However,more well-designed studies are required to solve the bone fragility puzzle in CLD patients.

Managing osteoporosis in ulcerative colitis: Something new?

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX® tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a long-term bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric and diaphyseal femoral fractures. UC is a long-lasting disease and the majority of patients is relatively young. In this scenario primary prevention of fragility fracture is the best cost-effective strategy. Vitamin D supplementation, adequate calcium intake, suitable physical activity (when possible), removing of risk factors for osteoporosis like smoking, and avoiding falling are the best medical acts.

Updated bone mineral density status in Saudi patients with inflammatory bowel disease

BACKGROUND Little is known about inflammatory bowel disease(IBD)burden and its impact on bone mineral density(BMD)among adult patients in Saudi Arabia.To the best of our knowledge,our study is the only study to give an update about this health problem in adult Saudi patients with IBD.IBD is a great risk factor for reduced BMD due to its associated chronic inflammation,malabsorption,weight loss and medication side effects.Consequently,screening for reduced BMD among patients with IBD is of utmost importance to curb and control anticipated morbidity and mortality among those patients.AIM To assess the relationship between IBD and BMD in a sample of adult Saudi patients with IBD.METHODS Ninety adult patients with IBD-62 Crohn’s disease(CD)and 28 ulcerative colitis(UC)-were recruited from King Fahad Specialist Hospital gastroenterology clinics in Buraidah,Al-Qassim.All enrolled patients were interviewed for their demographic information and for IBD-and BMD-related clinical data.All patients had the necessary laboratory markers and dual-energy x-ray absorptiometry scans to evaluate their BMD status.Patients were divided into two groups(CD and UC)to explore their clinical characteristics and possible risk factors for reduced BMD.RESULTS The CD group was significantly more prone to osteopenia and osteoporosis compared to the UC group;44%of the CD patients had normal BMD,19%had osteopenia,and 37%had osteoporosis,while 78%of the UC patients had normal BMD,7%had osteopenia,and 25%had osteoporosis(P value<0.05).In the CD group,the lowest t-score showed a statistically significant correlation with body mass index(BMI)(r=0.45,P<0.001),lumbar z-score(r=0.77,P<0.05)and femur z-score(r=0.85,P<0.05).In the UC group,the lowest t-score showed only statistically significant correlation with the lumbar z-score(r=0.82,P<0.05)and femur z-score(r=0.80,P<0.05).The ROC-curve showed that low BMI could predict the lowest t-score in the CD group with the best cut-off value at≤23.43(m/kg2);area under the curve was 0.73(95%CI:0.59–0.84),with a sensitivity of 77%,and a specificity of 63%.CONCLUSION Saudi patients with IBD still have an increased risk of reduced BMD,more in CD patients.Low BMI is a significant risk factor for reduced BMD in CD patients.

Bone mineral density in fracture neck of femur patients:What's the significance?

BACKGROUND The National Institute for Health and Care Excellence(NICE)guidelines have advised further research is required into investigating the added prognostic value of bone mineral density(BMD)in the assessment of fracture risk with the Fracture Risk Assessment Tool(FRAX)score.AIM To investigate the significance of BMD in fracture neck of femur patients and compare it to the outcome of the FRAX score.METHODS Inclusion criteria for this study were all patients who underwent dual-energy Xray absorptiometry(DXA)scan following fracture neck of femur between 2015 and 2017.Analysis of BMD,FRAX scores and patient demographic data was undertaken.RESULTS A total of 69 patients were included in the study,mean age 74.1 years.There was no significant difference between mean BMD of the femoral neck in males(0.65)as compared to females(0.61)(P=0.364).Analyses showed no significant correlation between BMD and menopause age(rs=-0.28,P=0.090).A significant difference was seen of the femoral neck BMD between the different fracture pattern types(P=0.026).A stronger correlation was observed between BMD of femoral neck and FRAX major score(rs=-0.64,P<0.001)than with BMD of lumbar spine and FRAX major score(rs=-0.37,P=0.003).CONCLUSION This study demonstrated that BMD of the femoral neck measured by DXA scan is of added prognostic value when assessing patients for risk of fracture neck of femur in combination with the FRAX predictive scoring system.

A novel non-invasive method for predicting bone mineral density and fracture risk using demographic and anthropometric measures

Fractures are costly to treat and can significantly increase morbidity.Although dual-energy x-ray absorptiometry(DEXA)is used to screen at risk people with low bone mineral density(BMD),not all areas have access to one.We sought to create a readily accessible,inexpensive,high-throughput prediction tool for BMD that may identify people at risk of fracture for further evaluation.Anthropometric and demographic data were collected from 492 volunteers(♂275,♀217;[44-20]years;Body Mass Index(BMI)=[27.6-6.0]kg/m^(2))in addition to total body bone mineral content(BMC,kg)and BMD measurements of the spine,pelvis,arms,legs and total body.Multiple-linear-regression with step-wise removal was used to develop a two-step prediction model for BMC followed by BMC.Model selection was determined by the highest adjusted R2,lowest error of estimate,and lowest level of variance inflation(α=0.05).Height(HTcm),age(years),sex^(m=1,f=0),%body fat(%fat),fat free mass(FFMkg),fat mass(FMkg),leg length(LLcm),shoulder width(SHWDTHcm),trunk length(TRNKLcm),and pelvis width(PWDTHcm)were observed to be significant predictors in the following two-step model(p<0.05).Step1:BMC(kg)=(0.0063×HT)+(-0.0024×AGE)+(0.1712×SEX^(m=1,f=0))+(0.0314×FFM)+(0.001×FM)+(0.0089×SHWDTH)+(-0.0145×TRNKL)+(-0.0278×PWDTH)-0.5073;R^(2)=0.819,SE-0.301.Step2:Total body BMD(g/cm^(2))=(-0.0028×HT)+(-0.0437×SEX^(m=1,f=0))+(0.0008×%FAT)+(0.2970×BMC)+(-0.0023×LL)+(0.0023×SHWDTH)+(-0.0025×TRNKL)+(-0.0113×PWDTH)+1.379;R^(2)=0.89,SE-0.054.Similar models were also developed to predict leg,arm,spine,and pelvis BMD(R^(2)=0.796-0.864,p<0.05).The equations developed here represent promising tools for identifying individuals with low BMD at risk of fracture who would benefit from further evaluation,especially in the resource or time restricted setting.

Mechanisms for increased systemic fracture risk after index fracture

The single best predictor of future fracture risk is a prior fracture at any skeletal site.However,the mechanisms underlying this relationship remain incompletely understood.Here we review three potential mechanisms underlying increased risk.An index fracture may reflect preexisting deficits in bone quality or impairments in physical function.Second,fracture may cause biomechanical changes that increase future fracture risk.Third,fracture induces a period of systemic bone loss that is never fully recovered.Further investigation into these mechanisms can inform treatments that prevent future fractures for individuals with a prior history of fracture.

Effect of BMI on outcomes of surgical treatment for tibial plateau fractures： A comparative retrospective case series study

Purpose： Tibia plateau fracture （TPF） treatment aims at achieving a stable, aligned, mobile, painless knee and preventing post-traumatic osteoarthritis. To achieve this goal, surgeons consider criteria such as patients＇ characteristics, severity, risk of complications, fracture displacementJdepression, degree of soft tissue injury. However, body mass index （BMI） is not considered as a risk factor in literature. Our study was conducted to find out any possible correlation between BMI and functional scores or radiological score separately. Methods： Retrospective analysis of case series between 2011 and 2014 was done on the database of a tertiary hospital in Istanbul. There were 67 TPF patients （54 males, 13 females） in the study. Relationship between BM1 and functional knee scores or radiological score was compared statistically. Closed fractures with both high-energy and low-energy injury were included in the study. Patients with open fracture, multi-trauma presence, meniscus and/or ligamentous injury, increased co-morbidity, inadequate records （25 cases in all） were excluded. Surgery type, Schatzker classification, injury side, trauma energy, and gender were considered as possible risk factors. Binary regression analysis was done for possible factors affecting functional knee scores and radiologic score. Results： Model summary calculations were done as Nagelkerke R2 test for Knee Society score, Lysholm knee score, and Ahlback and Rydberg radiologic scores, which were 0.648, 0.831, and 0.327 respec- tively. Homer-Lemeshow test values were 0.976, 0.998, and 0.362, respectively. There is negative correlation between BMI and both knee function scores. There is no correlation between BMI and radiologic score. Conclusion： An increase in BMI has a negative effect on functional knee scores after surgical treatment of TPFs. Therefore, BMI should be considered as a risk factor for surgical treatment of TPFs.