Increase In Fragility Fractures Research Articles

The effect of a post-anaesthesia high-care unit (PAHCU) admission on mobilization, length of stay and in-hospital mortality post-surgery in low energy neck of femur fracture patients

Purpose/aimWith an ageing population and an increase in fragility fractures of the hip (FFH), the role of an anaesthetist is evolving to include more peri-operative care. A post-anaesthesia high-care unit (PAHCU) should enhance care in post-operative patients. To our knowledge, there are no studies that have investigated the effect of a PAHCU admission on post-operative outcomes after FFH. This study aimed to compare post-operative outcomes of FFH patients admitted to PAHCU versus a standard post-operative orthopaedic ward (POOW).MethodologyA retrospective cohort study was conducted on adult patients with FFH who underwent surgery between January 2019 and December 2020 at our institution. Data were sourced from electronic medical records. SPSS version 28 was used to analyse data.ResultsA total of 231 patients were included. The PAHCU group (n = 35) displayed a higher burden of chronic illness and higher peri-operative risk scores as compared to the POOW group (n = 196). Median time to mobilize (TTM) in PAHCU was 84 h vs. 45 h in POOW group (p = 0.013). Median length of stay (LOS) in PAHCU was 133 h vs. 94 h in POOW (p = 0.001). The in-hospital mortality was 2.9% (n = 1) for PAHCU and 3.6% (n = 7) for POOW (p = 1). The 30-day mortality was 11.8% (n = 4) for PAHCU and 10.1% (n = 19) in POOW.ConclusionPAHCU admission resulted in delayed time to surgery and TTM, together with prolonged LOS, compared to those managed in POOW. However, these mortality rates remained comparable in both groups. This study contributes valuable insights into post-operative care of FFH patients in a resource-poor setting.

Fractures in sub-Saharan Africa: epidemiology, economic impact and ethnography (Fractures-E3): study protocol

Background: The population of older adults is growing in sub-Saharan Africa. Ageing exponentially increases fragility fracture risk. Of all global regions, Africa is projected to observe the greatest increase in fragility fractures. Fractures cause pain, disability and sometimes death, and management is expensive, often requiring complex healthcare delivery. For countries to plan future healthcare services, understanding is needed of fracture epidemiology, associated health service costs and the currently available healthcare resources. Methods: The Fractures-E3 5-year mixed-methods research programme will investigate the epidemiology, economic impact, and treatment provision for fracture and wider musculoskeletal health in The Gambia, South Africa and Zimbabwe. These three countries are diverse in their geography, degree of urbanisation, maturity of health service infrastructure, and health profiles. The programme comprises five study types: (i) population-based cross-sectional studies to determine vertebral fracture prevalence. Secondary outcomes will include osteoarthritis and sarcopenia. Age- and sex-stratified household sampling will recruit 5030 adults aged 40 years and older; (ii) prospective cohort studies in adults aged 40 years and older will determine hip fracture incidence, associated risk factors, and outcomes over one year (e.g. mortality, disability, health-related quality of life); (iii) economic studies of direct health costs of hip fracture with projection modelling of future national health costs and cost-effectiveness analyses of different hip fracture care pathways; (iv) national surveys of hip fracture services (including traditional bonesetters in The Gambia); and (v) ethnographic studies of hip fracture care provision and experiences will understand fracture service pathways. Conclusions: Greater understanding of current and expected fracture burdens, fracture risk factors, and existing fracture care provision, is intended to inform national clinical guidelines, health service policy and planning and future health service development in sub-Saharan Africa.

Adverse events with quetiapine and clarithromycin coprescription: A population-based retrospective cohort study.

Quetiapine is an atypical antipsychotic predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. We studied the risk of adverse events following coprescription of clarithromycin (a strong CYP3A4 inhibitor) versus azithromycin (not a CYP3A4 inhibitor) in quetiapine users. This was a population-based retrospective cohort study from 2004 to 2020 in Ontario, Canada in adult quetiapine users newly co-prescribed clarithromycin (n = 16,909) or azithromycin (n = 25,267). The primary outcome was the composite of hospital encounters with encephalopathy (defined as a diagnosis of delirium, disorientation, transient alteration of awareness, transient ischemic attack, or unspecified dementia), a fall, or a fracture within 30 days of new coprescription. Secondary outcomes were individual components of the composite outcome, hospital encounter with computed tomography(CT) head scan, and all-cause mortality. Coprescription of clarithromycin versus azithromycin with quetiapine was associated with a higher risk of the primary composite outcome (365 of 16,909 clarithromycin users [2.2%] vs. 309 of 16,929 azithromycin users [1.8%]; absolute risk increase, 0.34% [95% confidence interval,CI, 0.04-0.63]; relative risk [RR], 1.19 [95% CI,1.02-1.38]). This was primarily driven by an increase in fragility fractures (78 of 16,909 clarithromycin users [0.5%] vs. 45 of 16,923 azithromycin users [0.3%]; absolute risk increase, 0.20% [95% CI, 0.07-0.32]; RR, 1.74 [95% CI, 1.21-2.52]). Hospital encounters with a CT head scan were higher in clarithromycin users (220 of 16,909 [1.3%] vs. 175 of 16,923 azithromycin users [1.0%]; absolute risk increase, 0.27% [95% CI, 0.04-0.50]; RR, 1.26 [95% CI, 1.04-1.54]), but there was no difference in hospital encounters with encephalopathy, falls, or all-cause mortality between macrolide groups. Among adults taking quetiapine, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically greater 30-day risk of a hospital encounter for encephalopathy, falls, or fracture, which was predominantly related to a higher rate of fragility fractures.

Osteoporosis: Spotlight on current approaches to pharmacological treatment.

Despite the availability of safe and effective anti-osteoporosis treatments, osteoporosis continues to be undertreated. The increase in fragility fractures, which is the main clinical consequence of osteoporosis, is a major problem for healthcare systems of countries. A broad range of drugs including antiresorptive and anabolic agents are used in the pharmacological treatment of osteoporosis. Fracture risk assessment in drug selection is of utmost importance in terms of guiding treatment. The recommended thresholds for osteoporosis treatment decision making are based on major osteoporotic and hip fracture probabilities from the Fracture Risk Assessment Tool (FRAX®). Currently, antiresorptive agents are usually the first choice to increase bone mineral density (BMD) and reduce the fracture risk. Bisphosphonates and antiresorptive drugs such as denosumab, a nuclear factor kappa-B ligand (RANKL) inhibitor, are the most widely used drugs in the treatment of osteoporosis. Bisphosphonates alone are unlikely to provide long-term protection against fracture and restore BMD in patients with severe osteoporosis and high fracture risk. In such patients, treatment with an anabolic agent such as teriparatide, abaloparatide, or romosozumab should be ideally initiated to achieve maximal gain in bone mass and preserve the microarchitecture. Ideally, an antiresorptive drug should be continued to maintain gain in bone mass.

Assessing the intimate mechanobiological link between human bone micro-scale trabecular architecture and micro-damages

The dramatic increase in fragility fractures and the related health and economic burden rise the urge of a cutting-edge perspective to anticipate catastrophic fracture propagation in human bones. Recent studies address the issue from a multi-scale perspective, elevating the micro-scale phenomena as the key for detecting early damage occurrence. However, several limitations arise specifically for defining a quantitative framework to assess the contribution of lacunar micro-pores to fracture initiation and propagation. Moreover, the need for high resolution imaging imposes time-demanding post-processing phases. Here, we exploit synchrotron scans in combination with micro-mechanical tests, to offer a fracture mechanics-based approach for quantifying the critical stress intensification in healthy and osteoporotic trabecular human bones. This is paired with a morphological and densitometric framework for capturing lacunar network differences in presence of pathological alterations. To address the current time-consuming and computationally expensive manual/semi-automatic segmenting steps, we implement convolutional neural network to detect the initiation and propagation of micro-scale damages. The results highlight the intimate cross talks between toughening and weakening phenomena at micro-scale as a fundamental aspect for fracture prevention.

Bioinspired mineral hydrogels as nanocomposite scaffolds for the promotion of osteogenic marker expression and the induction of bone regeneration in osteoporosis

Osteoporosis is one of the most prevalent age-related diseases worldwide and is characterized by a systemic deterioration of bone strength (bone mineral density and bone quality) with a resulting increase in fragility fractures. Due to the complex osteoporotic pathological environment, it is a huge challenge to induce bone regeneration under osteoporosis conditions. In this study, we successfully nanoengineer a bioinspired mineralized hydrogel from the supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity. We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro. Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffolds for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in the osteoporotic rabbit model. Without the delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environments. Therefore, this work presents a type of bioinspired multifunctional mineral hydrogel that offers an alternative strategy to manage osteoporosis. Statement of Significance•We successfully nanoengineer a bioinspired mineralized hydrogel from supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity.•We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro.•Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffold for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in osteoporotic rabbit model. Without delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environment.

Quantitative Ultrasound - An Epidemiological Tool to Uncover the Influence of Lifestyle Factors & its Associated Co Morbidities on Bone Density

Osteoporosis, the metabolic disorder has become a global epidemic1 with increase in life expectancy and changing life style. Quantitative ultrasound is a cheap, non invasive, portable and convenient method to estimate bone strength without any radiation hazard.2–5 The aim of our study is to estimate the bone mineral density by using quantitative ultrasound, look for the influence of parameters like lifestyle factors, comorbidities, chronic drug intake, and other risk factors on BMD; and compare the results with those in the literature done with DEXA scans. In our study of 516 subjects, (i) BMD measures varied from -5.6 to +.5.55 with a mean of -1.8. (ii) BMD decreased significantly with age (r=.351, p<0.0001), (iii) Low BMD was associated with increase in Fragility fractures (p=.007) (iv) Antacid intake, which was pretty common in our subjects (28.7%) led to decrease in BMD (p<.005). (v) Diabetes significantly reduced BMD (p<.005). (vi) Increase in BMI led to significant increase in BMD (r=.166, p<.0001). (vii) BMD increased significantly with increase in physical activity (r=.148, p<.001). Most of the associations found in our study, except that with diabetes, were similar to those consistently associated with BMD as measured with DEXA scans.6–15 Our study suggests the use of Quantitative ultrasound as powerful epidemiological tool with similar outcome measures to DEXA scan without any radiation hazards.

Vertebral fractures, function and cognitive status in osteoporotic hip fractured women: The FOCUS study

IntroductionOsteoporosis is characterized by low bone mass and microarchitectural modifications of bone tissue, with a consequent increase in fragility fractures. Vertebral fractures (VF) are the most prevalent osteoporotic fractures and osteoporotic hip fractures are the most serious complication of osteoporosis. The objectives of the present study were to determine the prevalence of VF in osteoporotic hip fractured women and to evaluate their association with pre-existing factors such as activities of daily living, quality of walking, numbers of falls, cognitive aspects and comorbidities. Material and methodsTwenty-five departments of Orthopaedics, Rehabilitation and Geriatrics participated in the present cross-sectional observational study. Data for 916 osteoporotic hip fractured women were collected, including spine X-ray morphometry, pre-fracture Functional Ambulation Category (FAC), RANKIN scale, Short portable Mental Status Questionnaire (SPMSQ), Instrumental Activities of Daily Living (IADL), ADL, Cumulative Illness Rating Scale (CIRS), history of falls in the last 12 months and serum 25(OH)D measure. ResultsVFs were present in 54% of hip fractured patients. The VF group showed worse scores regarding the pre-hip fracture values for RANKIN, CIRS, SPMSQ, IADL than the group with no VF. Multivariable logistic regression analysis showed a significant association between the presence of VF and family history of fragility fractures, patients’ history of fractures, height, previous osteoporosis treatment and RANKIN pre-fracture score. Subgroup (n=417) analysis showed a strong association between 25(OH)D levels and CIRS with the presence of VF. ConclusionsPrevious VF are a common issue in osteoporotic hip fractured patients and negatively influence outcome measures in these patients.

Medical management of osteoporosis and the surgeons' role

Osteoporosis is a worldwide public health issue and with the aging population the resultant increase in fragility fractures has generated a significant socioeconomic impact. Robust scientific research has increased our knowledge of the endocrine mechanisms and pathophysiology of osteoporosis. This information has led to Level 1 randomized clinical trials which demonstrate the beneficial effects of appropriate regimens in reducing the fracture risk and the coincident mortality. Despite these contributions the public health problem remains and has stubbornly failed many public awareness campaigns by governmental and private professional organizations.Effectiveness in delivering the message is greatly enhanced following the sentinel fragility fracture whether it be distal radius, hip, or spine. The treating orthopedic surgeon has the full attention of the injured patient who can be steered into osteoporosis screening programs and ultimately treatment. Studies in Canada have shown that if the surgeon initiates the process by so much as ordering the bone densitometry exam the patient is more likely to get treatment for their underlying disease than if it is just suggested that the patient see their medical doctor at some future date. The patient takes the cue from the surgeon. Patient compliance goes up and the treatment is instituted.We as surgeons must be part of the solution. This has been emphasized in the worldwide efforts in orthopedic surgery such as the “Bone and Joint Decade” and “Own the Bone” programs. This commitment to bone health and restoration is important. Our patients deserve no less.

Pluripotent Stem Cells and Skeletal Regeneration--Promise and Potential.

The bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical-size defects, malformations, and tumor destruction may exceed the skeleton's capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore, the ability to generate large numbers of patient-specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts.

Ultrasonometric Profiling of Incidence and Risk of Osteoporosis in Rural Women

ABSTRACT Background: It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly aging population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. This investigation profiled the incidence and risk of osteoporosis in adult women from a rural setting using ultrasonic bone scanning technology. Methods: Between 2001 and 2005, adult female subjects (n = 323) in the age range of 40–87 were drawn from an independent, community dwelling, convenience sample. Bone mineral density T-scores were evaluated using heel ultrasonometry. Demographic and risk factor data, Merck Osteoporosis Evaluation SCORE questionnaire data, and the Osteoporosis Risk Assessment questionnaire data were analyzed. Results: Results of these scans indicate that 25% of the total population had a T-score ≤ −1.0, implying a 1.5-to 2.0-fold increase in risk ratio of hip or spinal fracture for each standard deviational decrease. Age at menopause and weight had a positive correlation with T-scores. While the overall scores on the Merck SCORE questionnaire were inversely correlated to T-scores, no significant correlation was found between the Osteoporosis Risk Assessment questionnaire and T-score data. Additionally, women who had taken estrogen had significantly higher T-scores (p = 0.038) than those who had not. Conclusion: That approximately 25% of this sample has low bone mass or osteoporosis underscores the importance of early screening in order to develop preventative awareness and provide education on bone health management. This finding has particularly important ramifications, since the sample was rural women, who typically have limited access to diagnostic bone density procedures.

Maintaining the life-long vitality and integrity of skeletal tissue

Although decreased bone strength and a consequent increase in fragility fractures has been regarded as an inevitable consequence of aging, there is great variability in this process. Moreover there are new findings concerning the mechanisms by which the skeleton maintains it vitality and integrity that should change this view. There are four basic mechanisms that can lead to decreased bone mass and strength and an increase in fragility fractures. 1) Genetic and lifestyle factors that impair the ability to achieve optimal peak bone mass and strength during childhood and adolescence. 2) Loss of bone mass and microarchitectural deterioration due to increased bone resorption, for which estrogen deficiency is probably the most important cause. 3) Inadequate bone formation during remodeling, which appears to be age related but for which the specific causes are not known. 4) Increased propensity to fall and decreased mobility that may be associated both with age related impairment in neuromuscular function and the use of drugs that impair balance. Substantial advances have been made in our understanding of the bone remodeling cycle, particularly the interaction of osteoblasts and osteoclasts that initiates resorption. Inflammatory cytokines may be involved in this process, but their specific role in human osteoporosis has not been resolved. New information on the roles of osteocytes and the Wnt signaling pathway in the regulation of bone formation indicate that these may be critical in the regulation of skeleton vitality and integrity. Hence new interventions that affect regulators of bone growth and remodeling may be developed that can maintain skeletal tissue and prevent the development of osteoporosis and fragility fractures.

Osteoporosis: A still increasing prevalence

It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly elderly population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. In the European Union, in 2000, the number of osteoporotic fractures was estimated at 3.79 million. A baseline fracture is a very strong predictor of further fractures with 20% of patients experiencing a second fracture within the first year. The costs to health care services are already considerable and, on current trends, are predicted to double by 2050. The direct costs of osteoporotic fractures to the health services in the European Union in the year 2000 were estimated at €32 billion. Guidelines for the diagnosis and treatment of osteoporosis are available in many countries; however, implementation is generally poor despite the availability of treatments with proven efficacy. Programs to increase awareness of osteoporosis and its outcomes are necessary for healthcare specialists and the general public. Earlier diagnosis and intervention prior to the first fracture are highly desirable.

Novel Assessment of Bone Using Time-Resolved Transcutaneous Raman Spectroscopy

With fragility fractures increasing as the population ages, there is a need for improved means to estimate risk of fracture. We recorded Raman spectra of both the mineral and organic phases of bone transcutaneously, a technology with potential to enhance bone quality and fracture risk assessment. The current "gold standard" assessment of bone quality is BMD determined by DXA. However, this accounts for only 60-70% of bone strength. X-rays are absorbed by the mineral phase of bone, whereas the organic phase remains essentially invisible; however, bone strength is critically dependent on both phases. We report, for the first time, a Raman spectroscopic technique that analyses both phases of bone beneath unbroken skin by eliminating spectral components of overlying tissues. We used an 800-nm laser (1-kHz, 1-ps pulses) with a synchronized 4-ps Kerr gate with variable picosecond delay that effectively shuttered out photons from overlying tissues. We measured bone Raman spectra at a point 2 mm above the carpus from two mouse genotypes with extreme differences in bone matrix quality: wildtype and oim/oim (matched for age, sex, and weight). Typical depth was 1.1 mm. We repeated the measurements with overlying tissues removed down to bone. Oim/oim mice produce only homotrimeric collagen, which results in poorly mineralized bone tissue. The main spectral features were present from both bone phases. The spectral bands were in similar ratios when measured through the skin or directly from bone (in both genotypes). The band of the mineral phase (phosphate nu1) was smaller in oim/oim mice when measured directly from bone and through skin. The band associated with a particular vibrational mode of organic phase collagen (CH2 wag) showed a frequency shift between the genotypes. This novel technique allowed us, for the first time, to make objective transcutaneous spectral measurements of both the mineral and the organic phases of bones and distinguish between normal and unhealthy bone tissue. After further optimization, this technology may help improve fracture risk assessments and open opportunities for screening in anticipation of the predicted increase in fragility fractures.