Assessment of fracture risk in a cohort of Egyptian female Systemic Lupus erythematosus patients

Aim of the work

To assess the fracture risk in a cohort of Egyptian systemic lupus erythematosus (SLE) females in correlation to some disease variables.

Effect of parathyroidectomy on osteoporosis and bone metabolism

The presentation of patients with hyperparathyroidism has changed over the past decades with the routine use of multichannel serum electrolyte analyzers. Serum calcium abnormalities rather than overt symptoms prompt the evaluation for suspected hyperparathyroidism. It is rare to see a patient with cystic bone changes; instead it is more common to have subtle bone loss identified in the evaluation of bone mineral density. Parathyroidectomy is recommended in patients with osteoporosis. Since the effect of parathyroid hormone on bone is complex, the changes in bone metabolism following parathyroidectomy and the effect of parathyroidectomy on fracture risk are important factors to consider. Studies have yielded conflicting results regarding the questions of bone density and fracture risk, limited by small sample size and short follow-up periods. Recent investigations describe a subset of patients with bone disease that may benefit from early surgical intervention.     

Bone mineral content and bone density is lower in adolescents with type 1 diabetes: A brief report from the RESISTANT and EMERALD studies

To understand the effect of type 1 diabetes (T1D) on bone mineral content (BMC) and bone density (BMD), we studied 125 T1D adolescents and 80 pubertal stage matched controls. T1D was associated with lower whole-body BMC and BMD compared to controls, even when adjusted for age, sex and sex hormones.     

Fracture risk and bone mineral density in Turner syndrome

Bone health is a major lifelong concern in caring for women and girls with Turner syndrome (TS). There is an approximately 25% increase in fracture risk most of which is related to medium or high impact trauma. The long bones, especially of the forearm are predominantly affected. This fact may be due to a selective cortical bone deficiency in TS which is unrelated to hypogonadism. In addition, lack of adequate estrogen replacement can lead to trabecular bone deficiency and increase in vertebral compression fractures after age 45. Evaluation of bone density by dual X-ray absorptiometry (DEXA) is important, however, it should be used judiciously in TS in view of its inherent tendency to underestimate the bone density of people with short stature. Bone size-independent methods, such as QCT or volumetric transformation of DEXA data should be used in individuals shorter than 150 cm. Achieving optimal bone density is of critical importance for fracture prevention in TS, and should be pursued by timely introduction of hormone replacement therapy, adequate dose of estrogens during the young adult life, optimal calcium and vitamin D intake and regular physical exercise. In addition, other measures to prevent fall and trauma should be considered, including optimizing hearing and vision, avoiding contact sports and exercise to improve coordination.     

Bones and Crohn＇s：No benefit of adding sodium fluoride or ibandronate to calcium and vitamin D

AIM: To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn’s disease (CD).METHODS: Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4).RESULTS: One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% confidence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated.CONCLUSION: Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.     

Heavy Cannabis Use Is Associated With Low Bone Mineral Density and an Increased Risk of Fractures

PurposeTo investigate possible associations between recreational cannabis use and bone health in humans.MethodsCross-sectional study of individuals recruited from primary care in the UK between 2011 and 2013. Cases were regular smokers of cannabis divided into moderate (n = 56) and heavy user (n = 144) subgroups depending on whether they reported fewer or more than 5000 cannabis smoking episodes during their lifetime. Controls comprised 114 cigarette smokers.ResultsHeavy cannabis users had lower total hip bone mineral density (mean ± SD Z-score: −0.20 ± 0.9 vs +0.2 ± 0.9, P < .0005), lower spine bone mineral density (−0.5 ± 1.2 vs 0.0 ± 1.2, P < .0005), and lower body mass index (BMI; 26.5 ± 6.0 vs 29.0 ± 7.0, P = .01) than controls. Fracture rate was also increased in heavy users (rate ratio = 2.17; 95% confidence interval, 1.59-2.95; P < .001). When compared with controls, serum cross-linked C-telopeptide of type 1 collagen (CTX) concentrations were raised in heavy cannabis users (0.3 ± 0.1 vs 0.2 ± 0.1 pg/mL, P = .045), as were serum N-terminal propeptide of type 1 procollagen (P1NP) concentrations (47.1 ± 19.2 vs 41.2 ± 17.8 pg/mL, P = .01). Serum total 25-hydroxyvitamin D concentrations were reduced in heavy users compared with controls (25.3 ± 16.8 vs 36.9 ± 26.7 nmol/L, P = .002). Multiple regression analysis revealed that heavy cannabis use was an independent predictor of spine bone mineral density, accounting for 5.4% of the variance (P = .035), and total hip bone mineral density, accounting for 5.8% of the variance (P = .001), but mediation analysis suggested that the effect on spine bone mineral density was indirect and mediated through low body mass index.ConclusionsHeavy cannabis use is associated with low bone mineral density, low BMI, high bone turnover, and an increased risk of fracture. Heavy cannabis use negatively impacts on bone health both directly and indirectly through an effect on BMI.     

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes

Background and aimsBone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice.Methods and resultsThe presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline.ConclusionsThe clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed.     

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 followup 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 longterm 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 anddiaphyseal 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.     

Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients

Aim of the work

To investigate the bone mineral density (BMD) in rheumatoid arthritis (RA) Tunisian patients, to identify the risk factors associated with its decrease and to assess the fracture risk.

Incidence of joint symptoms and bone fractures in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole

Purpose  Incidence of joint symptoms and bone fractures as well as changes in bone mineral density (BMD) in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole were investigated to determine whether there is an ethnic difference from Caucasian patients in the incidence of these adverse events of anastrozole. Methods  Adjuvant anastrozole was used to treat 348 postmenopausal breast cancer patients for a median period of 22 months. Adverse events of anastrozole including joint symptoms, loss of BMD, and bone fracture were investigated by means of chart review. Results  Joint symptoms developed in 96 (27.5%) patients. Age (younger than 65) and prior chemotherapy was strongly associated with an increased risk of joint symptoms. Annual fracture incidence was 0.86 and 0.85% and lumbar BMD decreased by 1.3 and 2.8% at 1 and 2 years, respectively. In comparison, the ATAC trial reported corresponding figures of 2.0 and 2.7 and of 2.2 and 4.0%. Conclusion  Incidence and risk factors of joint symptoms are similar for Japanese and Caucasian patients, but the former tend to show a smaller decrease in BMD and a lower incidence of bone fractures, probably due to ethnic difference in the hormonal milieu.     

Biochemical markers of bone turnover as predictors of osteoporosis and osteoporotic fractures in men and women: 10-year follow-up of the Taiji cohort

Abstract

We aimed to assess the capacity of biochemical markers of bone turnover (BTMs) to predict bone loss, osteoporosis (OP), and osteoporotic fractures. We randomly selected 400 individuals (age 40–79 years in 1993; 50 of each gender and age stratum) from a list of registered residents. In the years 1993, 1996, 2000, and 2003, bone mineral density (BMD) of the spine and hip were measured by dual-energy X-ray absorptiometry. The BTMs assessed at baseline were serum intact osteocalcin (OC), total OC, bone-specific alkaline phosphatase, C-terminal propeptide of type I procollagen, N-terminal propeptide of type I procollagen (PINP), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinase, C-terminal cross-linking telopeptide of type I collagen (beta-CTX), N-terminal cross-linking telopeptide of type I collagen (NTX), urinary pyridinoline, and deoxypyridinoline (DPD). For 307 completers, multivariate analysis after adjusting for confounders revealed that serum PINP levels in men [hazard ratio (HR) 2.80, P < 0.05] and serum PINP (HR 1.65, P < 0.05), beta-CTX (HR 1.80, P < 0.001), NTX (HR 1.96, P < 0.01), and urinary DPD levels (HR 1.40, P < 0.05) in women were significantly related to the occurrence of spinal OP. In addition to adjustment for the baseline status of BMD, i.e., osteopenia or normal range, PINP, beta-CTX, and NTX in women could significantly predict the future occurrence of spinal OP. BTMs were not significant predictors of bone loss, femoral OP, or osteoporotic fractures. In conclusion, various BTMs in women can predict the occurrence of spinal OP.     

Assessment of risk factors for bone fractures in patients with type 2 diabetes mellitus: A study in Saudi Arabia

Background and aimsThis study aimed to estimate the prevalence of bone fractures and analyze their associated risk factors in people with and without type 2 diabetes (T2D) in Saudi Arabia.MethodsThis study was conducted among 1188 people (581 type 2 diabetes) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. In addition to the demographic variables, glycated hemoglobin (HbA1c), creatinine, estimated glomerular filtration rate (eGFR), use of teriparatide, presence of rheumatoid arthritis, presence of chronic obstructive pulmonary disease (COPD), Bone mineral density (BMD), Trabecular Bone Score (TBS) and Fracture Risk using the Fracture Risk Assessment Tool (FRAX) were also collected.ResultsThere were 1188 people (mean age 66.5 ± 8.7yrs) included in this study, of which 1068 (89.9%) were female, and 120 (10.1%) were male. A total of 112 (9.4%) individuals had a fracture history. Female, use of teriparatide, TBS (partially degraded and degraded), FRAX with TBS (MOF), and FRAX with TBS (Hip fx) were identified as independent risk factors for fracture in the whole study population. Teriparatide use and FRAX with TBS (MOF) were observed as independent risk factors for fracture in the non-diabetic population, whereas age, creatinine, eGFR, teriparatide, osteopenia, osteoporosis, TBS (partially degraded, degraded), FRAX with TBS (MOF), FRAX with TBS (Hip fx) were determined as independent risk factors for fracture among patients with diabetes.ConclusionPatients with T2D were observed to have a higher risk for fractures. The findings of the study highlight the requirement for fracture prevention strategies in patients with diabetes.     

Impact of Diabetes and its Treatment on Bone

Type 2 diabetes (T2DM) is associated with increased fracture risk and higher bone density (BMD), suggesting that diabetic bone is more fragile for a given density. The changes in bone quality that accompany T2DM are still not fully delineated but potential factors include more rapid bone loss, differences in cortical bone and bone structure, and changes in material properties of bone collagen due to accumulation of advanced glycation endproducts (AGEs). Increased fracture risk appears to be concentrated among patients with longer duration of diabetes while those with recent onset or with impaired glucose tolerance may instead be protected from fracture risk. Characteristics of T2DM have contradictory effects on bone strength and fracture risk. Bone strength is generally increased with larger body size and hyperinsulinemia. Features of T2DM that lead to increased bone fragility are not clearly understood but are likely to include hyperglycemia. Higher levels of glucose result in the accumulation of AGEs. In addition, hyperglycemia may have direct and indirect effects on osteocytes, osteoblasts, and osteoclasts resulting in weaker bone. Treatment of T2DM may have generally favorable effects on bone through improvements in glycemic control. However, use of thiazolidinediones (TZDs) in particular causes increased fracture risk in women, due to decreased bone formation and increased bone loss. In sum, substantial evidence now indicates that T2DM results in bone that is more fragile for a given BMD. Further research is needed to understand the specific changes in diabetic bone that cause reduced strength, to clarify the effects of hyperglycemia, and to identify other factors associated with T2DM that reduce bone quality.     

Assessing Fracture Risk and Effects of Osteoporosis Drugs: Bone Mineral Density and Beyond

Although there have been numerous advances in the assessment of bone strength and fracture risk, the majority of these techniques can only be performed in research laboratories, making them largely unavailable to practicing clinicians. Prospective epidemiologic studies have identified risk factors that can be assessed within the clinic and combined with bone mineral density to allow clinicians to better identify untreated individuals at heightened risk for fracture and to make informed treatment decisions based on 10-year absolute fracture risk. This article discusses the assessment of fracture risk in clinical practice, reviews currently and soon-available bone measurement tools, and details the impacts of osteoporosis therapies on fracture risk.     

A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children

Objective

To summarize the published effects of systemic glucocorticoid therapy on bone mineral density (BMD) and fractures in children.

Methods

We performed a systematic review and meta-analysis of existing literature, using Medline, CINAHL, and Cochrane databases to identify studies of BMD or fractures in children ≤18 years taking systemic glucocorticoid therapy. We excluded studies of inhaled glucocorticoids, chemotherapy, and organ transplantation. Two authors reviewed abstracts for inclusion, read full-text articles to extract data, and rated each study using the Downs–Black scale.

Results

A total of 16 studies met eligibility criteria, including 10 BMD (287 children) and six fracture (37,819 children) studies. Spine BMD was significantly lower (−0.18; 95% CI = −0.25; −0.10 g/cm²) in children taking glucocorticoid therapy, compared to age- and gender-matched healthy controls. Spine BMD was also lower (−0.14; 95% CI = −0.27; 0.00 g/cm²) in children taking glucocorticoids, compared to children with the same disease not taking glucocorticoids. Incident clinical fracture rates varied from 2% to 33%. Morphometric vertebral fracture incidence ranged from 6% to 10%, and prevalence was 29–45%.

Conclusion

Published data suggest that children treated with glucocorticoid therapy have lower spine BMD compared to healthy children. Whether children receiving glucocorticoid therapy have lower spine BMD compared to children with milder disease not requiring such therapy is not certain. Clinical and morphometric vertebral fractures are common, although only one study assessed fracture rates in healthy controls. Additional well-designed, prospective studies are needed to evaluate the skeletal effects of glucocorticoid therapy in children.     

Multi-disciplinary care of the patient with acute hip fracture: How to optimise the care for the elderly,traumatised patient at and around the time of the fracture to ensure the best short-term outcome as a foundation for the best long-term outcome

Of the 70,000 patients presenting in the UK each year with hip fracture, most are frail, elderly with multiple co-morbidities and polypharmacy. Falls are often attributed to slips or trips, but many reflect the patient's inability to steady themself because of slowed reflexes, poor balance, underlying musculoskeletal disorders, poor vision and sarcopenia. A proportion of patients fall due to an inter-current medical illness, such as chest or urinary sepsis and others from acute presentation of stroke or cardiac arrhythmia.These patients require a coordinated multidisciplinary approach from the point of admission to the point of discharge. The National Institute for Health and Care Excellence (NICE) Guidance on hip fracture published in 2011 refers to the hip fracture programme [1]. This chapter aims to expand on the concept of the hip fracture programme and how this approach in the acute peri-operative period can ensure the best short-term outcomes as a foundation for the best possible longer-term outcomes.     

Assessment of bone mineralization in children and adolescents

Bone mineral accrual during growth results in gender-, race-, and maturation-specific changes in trabecular and cortical density and dimensions. Children with chronic disease have multiple potential risk factors for impaired bone accrual. Risk factors include delayed growth and maturation, decreased weight-bearing activity, malnutrition, vitamin D deficiency, glucocorticoid therapy, impaired sex hormones and growth hormone, and increased bone resorption by inflammatory cytokines. The impact of chronic diseases may be immediate, resulting in childhood fragility fractures, or delayed, owing to suboptimal peak bone mass accrual and increased fracture risk with the inevitable bone loss during aging. Dual energy X-ray absorptiometry is, by far, the most frequent method for the assessment of bone health in children at risk. This assessment is hampered by lack of a agreement on the quantitative definition of osteopenia and osteoporosis in children, inadequate reference data, technical limitations in small children, and varied approaches to the interpretation of results in children with delayed growth and maturation. This review summarizes the expected gains in bone size, mass and strength during childhood and adolescence, the role of the bone—muscle unit, the advantages and disadvantages of the available technologies for the assessment of skeletal health in children, and possible alternative strategies for the assessment of bone healthy in children with delayed growth and maturation.     

Secondary prevention and estimation of fracture risk

The key questions addressed in this chapter are:? How can individual risk of fracture be best estimated?? What is the best system to prevent a further fracture?? How to implement systems for preventing further fractures?Absolute fracture risk calculators (FRCs) provide a means to estimate an individual's future fracture risk. FRCs are widely available and provide clinicians and patients a platform to discuss the need for intervention to prevent fragility fractures.Despite availability of effective osteoporosis medicines for almost two decades, most patients presenting with new fragility fractures do not receive secondary preventive care. The Fracture Liaison Service (FLS) model has been shown in a number of countries to eliminate the care gap in a clinically and cost-effective manner.Leading international and national organisations have developed comprehensive resources and/or national strategy documents to provide guidance on implementation of FLS in local, regional and national health-care systems.     

Predictors of Osteoporosis and Vertebral Fractures in Patients Presenting with Moderate-to-Severe Chronic Obstructive Lung Disease

Abstract

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < –2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.