Introduction. Fractures of the proximal humerus represent a major osteoporotic burden. Recent developments in CT imaging have emphasized the importance of cortical bone thickness distribution in the prevention and management of fragility fractures. We aimed to experimentally define the CT density of cortical bone in the proximal humerus for building cortical geometry maps. Methods. With ethical approval we used ten fresh frozen human proximal humeri. These were stripped of all soft tissue and high resolution CT images were then taken. The humeral heads were then subsequently resected to allow access to the metaphyseal area. Using curettes, cancellous bone was removed down to hard cortical bone. Another set of CT images of the reamed specimen was then taken. Using CT imaging software and a CAD interface we then compared cortical contours at different CT density thresholds to the reference inner cortical contour of our reamed specimens. Working with 3D model representations of these cortical maps, we were able to accurately make distance comparison analyses based on different CT thresholds. Results. We could compute a single closest value at 700HU. There was no difference found in the HU based contours generated along the 500HU–900HU pixels (p=1.000). The contours were significantly different to those generated at 300HU, 400HU, 1000HU and 1100HU. Discussion/conclusion: A Hounsfield range of 500 to 900 HU can accurately depict cortical bone geometry in the proximal humerus. Thresholding outside this range leads to statistically significant inaccuracies. Our results concur with a similar range reported in the literature for the proximal femur. Knowledge of regional variations in cortical bone thickness has direct implications for basic science studies on osteoporosis and its treatment, but is also important for the orthopaedic surgeon since our decision for treatment options is often guided by local bone quality

Low-energy fractures complications are a major public health issue that make osteoporosis even worse. In sub-Saharan Africa, the prevalence of osteoporosis varies from 18.2% to 65.8%. There was no change in bone mineral density between HIV-infected and non-HIV-infected women in Sub-Saharan Africa, where HIV is widespread. Other investigations that demonstrated that HIV-infected people had poor BMD both before and after starting anti-retroviral treatment did not consistently show a low BMD finding. Inflammation-mediated bone remodelling has been associated with low BMD in HIV-infected patients. Antiretroviral Therapy has been demonstrated to exacerbate bone loss in addition to the pre-existing intrinsic risk of developing osteoporosis. Question: Is there loss of bone in HIV-infected patients before initiating ART?. The patients who were HIV-positive and enrolled in the ADVANCE research were retrospectively reviewed on a desk. All of the 1053 individuals in the ADVANCE research had a DXA scan performed to evaluate BMD as part of the initial screening and recruitment approach. The ADVANCE research enrolled HIV-positive people and randomly assigned them to three ART arms. A total of 400 patients were reviewed. Of these 400 records reviewed, 62.3% were female. 80% of the participants were younger than 40 years old, and 3% were older than 50 years. 82% were virally suppressed with less than 50 viral copies. The prevalence of osteopenia was 25.5% and osteoporosis was 2.8%, observed in predominantly African female participants aged between 30 and 39 years. The findings of this study confirm that there is pre-existing bone loss among HIV-infected ART naïve individuals. Approximately 28.3% in our study had clinically confirmed evidence of bone loss and of these, 2.8% of the entire cohort had osteoporosis. Bone loss was most prevalent in black females who are virologically suppressed

Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

A hip fracture represents the extreme end of osteoporosis, placing a significant burden on secondary care, society, and the individual patient. The National Hip Fracture Database (NHFD) reports each hospital's attainment of the BPT with other measures, along with reporting outcomes. There is clearly wide variability in provision of orthogerriatrician (OG) services across the dataset. Unfortunately, despite overwhelming evidence that provision of an OG service is of benefit, it is presently challenging to recruit to this important specialty within the UK. Publicly available reports from the NHFD were obtained for each of the 177 participating hospitals for 2017. This was matched with information held within the annual NHFD Facilities Audit for the same period, which include hours of OG support for each hospital. This information was combined with a Freedom of Information request made by email to each hospital for further details concerning OG support. The outcome measures used were Length of Stay (LoS), mortality, and return to usual residence. Comparison was made with provision of OG services by use of Pearson's correlation coefficient. In addition, differences in services were compared between the 25% (44) hospitals delivering outcomes at the extremes for each measure. Attainment of BPT correlated fairly with LoS (−0.48) and to less of a degree with mortality (−0.1) and return home (0.05). Perioperative medical assessment contributed very strongly with BPT attainment (0.75). In turn perioperative medical assessment correlated fairly with LoS (−0.40) and mortality (−0.23) but not return home (0.02). Provision of perioperative medical assessment attainment was correlated fairly with total OG minutes available per new patient (0.22), total OG minutes available per patient per day (0.29) and number of days per week of OG cover (0.34); with no link for number of patients per orthogeriatrician (0.01). Mortality for the best units were associated with 30% more consultant OG time available per patient per day, and 51% more OG time available per patient. Units returning the most patients to their usual residence had little association with OG time, although had 59% fewer patients per OG, the best units had a 19% longer LoS. For all three measures results for the best had on average 0.5 days per week better routine OG access. There is no doubt that good quality care gives better results for this challenging group of patients. However, the interaction of BPT, other care metrics, level of OG support and patient factors with outcomes is complex. We have found OG time available per patient per day appears to influence particularly LoS and mortality. Options to increase OG time per patient include reducing patient numbers (ensuring community osteoporosis/falls prevention in place, including reducing in-patient falls); increasing OG time across the week (employing greater numbers/spreading availability over 7 days per week); and reducing LoS. A reduction in LoS has the largest effect of increasing OG time, and although it is dependent on OG support, it is only fairly correlated with this and many other factors play a part, which could be addressed in units under pressure

Hip fractures frequently occur in elderly patients with osteoporosis and are rapidly increasing in prevalence owing to an increase in the elderly population and social activities. We experienced several recent presentations of TFNA nails failed through proximal locking aperture which requires significant revision surgery in often highly co-morbid patient population. The study was done by retrospective data collection from 2013 to 2023 of all the hip fractures which had been fixed with Cephalomedullary nails to review and compare Gamma (2013–2017) and TFNA (2017–2023) failure rates and the timing of the failures. Infected and Elective revision to Arthroplasty cases were excluded. The results are 1034 cases had been included, 784 fixed with TFNA and 250 cases fixed Gamma nails. Out of the 784 patients fixed with TFNA, 19 fixation failed (2.45%). Out of the 250 cases fixed with Gamma nails, 15 fixation failed (6%). Mean days for fixation failure were 323 and 244 days in TFNA and Gamma nails respectively. We conclude that TFNA showed remarkable less failure rates if compared to Gamma nails. At point of launch, testing was limited and no proof of superiority of TFNA over Gamma nail. Several failures identified with proximal locking aperture in TFNA which can be related to the new design which had Substantial reduction in lateral thickness at compression screw aperture

One of the most important sequelae to ageing is osteoporosis and subsequently hip fractures. Hip fractures are associated with major morbidity, mortality and costs. Most patients require surgery to restore mobility. Provision of surgery and its complications is poorly understood in South Africa. Our aim was to collect and report current hip fracture care at four centres in South Africa, as well as reporting surgical and general patient outcomes. A three year retrospective cohort at four centres will be described, focussing on provision of surgical care, mortality, types of surgery and complications. We identified 562 patients who had surgical intervention for fragility fractures, 66% were females. Forty nine percent had open reduction and internal fixation, 28% had hemi-arthroplasty replacement whilst 23% had total hip replacements. Twenty percent of patients had operative intervention within 36 hours of presentation to the emergency department. Mortality was 9% at 30 days. The most common complications were lower respiratory infections (29%), urinary tract infections (21%) and surgical site infections (9%). This is the largest cohort of surgically treated hip fracture from South Africa. Proportions of patients receiving different surgical interventions such as THR are comparable to the broader literature. However a number of key performance indicators such as surgery within 36 hours are challenging to meet. Given the changing demographics of South Africa, this study provides an early insight to contemporary care and may help provide direction for broader national strategies for reporting and improving hip fracture care

There is conjecture on the optimal timing to administer bisphosphonate therapy following operative fixation of low- trauma hip fractures. Factors include recommendations for early opportunistic commencement of osteoporosis treatment, and clinician concern regarding the effect of bisphosphonates on fracture healing. We performed a systematic review and meta-analysis to determine if early administration of bisphosphonate therapy within the first month post-operatively following proximal femur fracture fixation is associated with delay in fracture healing or rates of delayed or non-union. We included randomised controlled trials examining fracture healing and union rates in adults with proximal femoral fractures undergoing osteosynthesis fixation methods and administered bisphosphonates within one month of operation with a control group. Data was pooled in meta-analyses where possible. The Cochrane Risk of Bias Tool and the GRADE approach were used to assess validity. For the outcome of time to fracture union, meta-analysis of three studies (n= 233) found evidence for earlier average time to union for patients receiving early bisphosphonate intervention (MD = −1.06 weeks, 95% CI −2.01 – −0.12, I. 2. = 8%). There was no evidence from two included studies comprising 718 patients of any difference in rates of delayed union (RR 0.61, 95% CI 0.25–1.46). Meta-analyses did not demonstrate a difference in outcomes of mortality, function, or pain. We provide low-level evidence that there is no reduction in time to healing or delay in bony union for patients receiving bisphosphonates within one month of proximal femur fixation

Background. Recently, a larger number of elderly individuals with osteoporosis has undergone total knee arthroplasty (TKA). Intuitively, such vulnerable bone condition should deteriorate post-TKA functional recovery compared to a non-osteoporotic condition, but this hypothesis has not been directly examined. Methods. To address this issue, we analysed prognosis of patients who underwent TKA in Toranomon Hospital in Japan between April 2016 and March 2017 (27 of 40 cases, age 75.0±8.2 years old, BMI 24.5±3.1), and evaluated effects of osteoporosis on the changes in functions of the knees three/six/twelve months after the operation. The knee functions were quantified based on Knee Society Score (KSS), and the severity of the pre-operative osteoporosis was evaluated by T-score. We examined the relationships between these scores using multiple regression analyses with age, BMI, and sex as covariates. We excluded patients with rheumatoid arthritis. Results. The multiple regression analyses revealed that the severity of osteoporosis (T-score) before TKA did not have sufficient explanatory powers for either type of KSS (for Knee Score, adjusted R2 ≤ 0.16; for Functional Score, adjusted R2 ≤ 0.15). In addition, Pearson correlation coefficients between the pre-operative osteoporosis severity and KSS were weak (for Knee Score, |r| < 0.07, P > 0.78; for Functional Score, |r| < 0.27, P > 0.21; Fig 1). This tendency was qualitatively preserved even when we repeated these analyses for each sex group. Conclusions. These analyses suggest that counterintuitively, pre-operative osteoporosis does not significantly deteriorate the functional outcome of TKA in the elderly population. Although longer observations of larger samples will be needed, the current findings indicate the possibility that we may not have to hesitate over TKA even for osteoporotic patients. For any figures or tables, please contact the authors directly

The widely used Fracture Risk Assessment Tool (FRAX) estimates a 10-year probability of major osteoporotic fracture (MOF) using age, sex, body mass index, and seven clinical risk factors, including prior history of fracture. Prior fracture is a binary variable in FRAX, although it is now clear that prior fractures affect future MOF risk differently depending on their recency and site. Risk of MOF is highest in the first two years following a fracture and then progressively decreases with time – this is defined as imminent risk. Therefore, the FRAX tool may underestimate true fracture risk and result in missed opportunities for earlier osteoporosis management in individuals with recent MOF. To address this, multipliers based on age, sex, and fracture type may be applied to baseline FRAX scores for patients with recent fractures, producing a more accurate prediction of both short- and long-term fracture risk. Adjusted FRAX estimates may enable earlier pharmacologic treatment and other risk reduction strategies. This study aimed to report the effect of multipliers on conventional FRAX scores in a clinical cohort of patients with recent non-hip fragility fractures. After obtaining Research Ethics Board approval, FRAX scores were calculated both before and after multiplier adjustment, for patients included in our outpatient Fracture Liaison Service who had experienced a non-hip fragility fracture between June 2020 and November 2021. Patients age 50 years or older, with recent (within 3 months) forearm (radius and/or ulna) or humerus fractures were included. Exclusion criteria consisted of patients under the age of 50 years or those with a hip fracture. Age- and sex-based FRAX multipliers for recent forearm and humerus fractures described by McCloskey et al. (2021) were used to adjust the conventional FRAX score. Low, intermediate and high-risk of MOF was defined as less than 10%, 10-20%, and greater than 20%, respectively. Data are reported as mean and standard deviation of the mean for continuous variables and as proportions for categorical variables. A total of 91 patients with an average age of 64 years (range = 50-97) were included. The majority of patients were female (91.0%), with 73.6% sustaining forearm fractures and 26.4% sustaining humerus fractures. In the forearm group, the average MOF risk pre- and post-multiplier was 16.0 and 18.8, respectively. Sixteen percent of patients (n = 11) in the forearm group moved from intermediate to high 10-year fracture risk after multiplier adjustment. Average FRAX scores before and after adjustment in the humerus group were 15.7 and 22.7, respectively, with 25% (n = 6) of patients moving from an intermediate risk to a high-risk score. This study demonstrates the clinically significant impact of multipliers on conventional FRAX scores in patients with recent non-hip fractures. Twenty-five percent of patients with humerus fractures and 16% of patients with forearm fractures moved from intermediate to high-risk of MOF after application of the multiplier. Consequently, patients who were previously ineligible for pharmacologic management, now met criteria. Multiplier-adjusted FRAX scores after a recent fracture may more accurately identify patients with imminent fracture risk, facilitating earlier risk reduction interventions

Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass. Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR. Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment. Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons

Rapidly progressive osteoarthritis of the hip (RPOH) is an unusual subset of osteoarthritis. It is characterized by rapid joint space loss, chondroly­sis, and sometimes marked femoral head and acetabular destruction as a late finding. The exact pathogenetic mechanism is unknown. Potential causes of RPOH include subchondral insufficiency fracture resulting from osteoporosis, increasing posterior pelvic tilt as a mechanical factor, and high serum levels of matrix metalloproteinase (MMP)-3 as biological factors. This study was aimed to identify some markers that associate with the destructive process of RPOH by analyzing the proposed pathological factors of the disease, MMP-3, pelvic tilt, and osteoporosis. Of female patients who visited our hospital with hip pain from 2012 through 2018, this study enrolled female patients with sufficient clinical records including the onset of hip pain, age and body mass index (BMI) at the onset, a series of radiographs during the period of >12 months from the onset of hip pain, and hematological data of MMP-3 and C-reactive protein (CRP). We found the hip joints of 31 patients meet the diagnostic criteria of RPOH, chondrolysis >two mm in one year, or 50% joint space narrowing in one year. Those patients were classified into two groups, 17 and 14 patients with and without subsequent femoral head destruction in one year shown by computed tomography, respectively. Serum MMP-3 and CRP were measured with blood samples within one year after the hip pain onset. The cortical thickness index (CTI) as an indicator of osteoporosis and pelvic tilt parameters were evaluated on the initial anteroposterior radiograph of the hip. These factors were statistically compared between the two groups. This study excluded male patients because RPOH occurs mainly in elderly females and the reference intervals of MMP-3 are different between males and females. There was no difference in age at onset or bone mass index between the RPOH patients with and without subsequent femoral head destruction. Serum levels of MMP-3 were significantly higher in the RPOH patients with the destruction (152.1 ± 108.9 ng/ml) than those without the destruction (66.8 ± 27.9 ng/ml) (P = 0.005 by Mann-Whitney test). We also found increased CRP in the patients with femoral head destruction (0.725 ± 1.44 mg/dl) compared with those without the destruction (0.178 ± 0.187 mg/dl) (P = 0.032 by Mann-Whitney test). No difference in the duration between the hip pain onset and the blood examination was found between the two groups. There was no significant difference in CTI or pelvic tilt between the two groups. The pathological condition that may increase serum MMP-3 and CRP could be involved in femoral head destruction after chondrolysis of the hip in patients with RPOH

Introduction. Distal femur fracture fixation in elderly presents significant challenges due to osteoporosis and associated comorbidities. There has been an evolution in the management of these fractures with a description of various surgical techniques and fixation methods; however, currently, there is no consensus on the standard of care. Non-union rates of up to 19% and mortality rates of up to 26 % at one year have been reported in the literature. Delay in surgery and delay in mobilisation post-operatively have been identified as two main factors for high rate of mortality. As biomechanical studies have proved better stability with dual plating or nail-plate combination, a trend has been shifting for past few years towards rigid fixation to allow early mobilisation. Our study aims to compare outcomes of distal femur fractures managed with either single plate (SP), dual plating (DP) or nail-plate construct (NP). Methods. A retrospective review of patients aged above 65 years with distal femur fractures (both native and peri-prosthetic) who underwent surgical management between June 2020 and May 2023 was conducted. Patients were divided into three groups based on mode of fixation - single plate or dual plating or nail-plate construct. AO/OTA classification was used for non-periprosthetic, and Unified classification system (UCS) was used for periprosthetic fractures. Data on patient demographics, fracture characteristics, surgical details, postoperative complications, re-operation rate, radiological outcomes and mortality rate were evaluated. Primary objective was to compare re-operation rate and mortality rate between 3 groups at 30 days, 6 months and at 1 year. Results. A cohort of 32 patients with distal femur fractures were included in this study. 91% were females and mean age was 80.97 (range 68–97). 18 (53%) were non-periprosthetic fracture and 14 (47%) were periprosthetic fractures.18 patients underwent single plate fixation (AO/OTA 33A – 8, 33B/C – 2, UCS V3B – 5, V3C – 3),10 patients had dual plate fixation (AO/OTA 33A – 1, 33B/C – 4, UCS V3B – 3, V3C – 2) and 4 patients underwent nail-plate combination fixation (AO/OTA 33A – 4). 70.5% patients had surgery within 36 hours of admission and 90% within 48 hours. Analysis showed no re-operation at 30 days, 6 months in all 3 groups. At 1 year one patient had re-operation in dual-plating periprosthetic group (Distal femur replacement done for failed fixation). Three patients (16%) in single plate group had re-operation at 2 years (2 for peri-implant fracture and 1 for infection). None of the patients treated with Nail-plate combination had re-operation. Mortality rate at 30 days was 0% in among all the 3 groups. At 6 months, it was 16% in single plate group and 0% in DP and NP groups at 6 months and at 1 year mortality rate was 27% in SP group, 10% in DP and 0% in NP group. Combined mortality rate was 0% at 30 days, 9% at 6 months and 18.7% at one year. Conclusion. Our analysis provides insights into fixation methods of distal femur fractures in elderly patients. We conclude that a lower re-operation rate and mortality rate can be achieved with early surgery and rigid fixation with either dual plating or nail-plate construct to allow early mobilisation. Further prospective studies are warranted to confirm these findings and guide the selection of optimal surgical strategies for these challenging fractures

In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis. All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area. Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia. This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss

Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect bone regeneration during impaired fracture healing under osteoporotic conditions. Therefore, this study investigates the effects of SP and α-CGRP on fracture healing and fracture-related pain processes under conditions of experimental osteoporosis using SP- and α-CGRP-deficient mice and WT controls. We ovariectomized female WT, Tac1−/− and α-CGRP−/− mice (age 10 weeks, all strains on C57Bl/6J background) and set intramedullary fixed femoral fractures in the left femora 28 days later. We analyzed pain threshold (Dynamic Plantar Aesthesiometer Test) and locomotion (recorded at day and night, each for 1 hour, EthoVision®XT, Noldus) at 5, 9, 13, 16 and 21 days after fracture. At each time point, fractured femora were prepared for histochemical analysis of callus tissue composition (alcian blue/sirius red staining). Pain threshold is significantly higher in Tac1−/− mice 13 days after fracture and tends to be higher after 21 days compared to WT controls. In contrast, touch sensibility was similar in α-CGRP−/− mice and WT controls but compared to Tac1−/− mice pain threshold was significantly lower in α-CGRP−/− mice 13 and 16 days and tends to be lower 21 days after fracture. Locomotion of Tac1−/− mice during daylight was by trend higher 9 days after fracture and significantly higher 16 days after fracture whereas nightly locomotion is reduced compared to WT mice. Analysis of locomotion during daylight or night revealed no differences between α-CGRP−/− and WT mice. During early fracture healing phase, 5 and 9 days after fracture, transition of mesenchymal to cartilaginous callus tissue tends to be faster in Tac1−/− mice compared to WT controls whereas no difference was observed during late stage of fracture healing, 13, 16 and 21 days after fracture. In contrast, callus tissue maturation seems to be similar in α-CGRP−/− and WT mice. Our data indicate different effects of SP and α-CGRP on fracture healing under conditions of experimental osteoporosis as a model for impaired bone tissue. Lack of α-CGRP seems to have no effects, but loss of SP affects locomotion throughout osteoporotic fracture healing and fracture-related pain processes during late phases of osteoporotic fracture healing. This indicates a modified role of SP during fracture healing under impaired versus healthy conditions, where SP changed early fracture-related pain processes and had no influence on callus tissue composition

In Alberta there are over 2,700 hip fractures per year costing the health system over $24 million in acute care costs alone. 50% of hip fracture patients have had a prior fragility fracture as a result of underlying osteoporosis (OP) that has never been assessed or appropriately treated. The Fracture Liaison Service (FLS) in Alberta aims to improve appropriate osteoporosis care, highlight and address gaps within seniors care through OP management, and provide a geriatric syndrome triage service. The FLS has developed a linkage with the Emergency Department (ED) geriatric team whereby hip fracture patients are identified in ED using a screening tool for geriatric syndromes prior to their surgery, allowing the FLS to follow through on comorbidities likely contributing to falls. An inpatient orthopaedic unit with a dedicated Registered Nurse (RN) and a Care of the Elderly Physician see and assess hip fracture patients after surgery for appropriate osteoporosis management and treatment. Screening tools have been developed to quickly detect underlying dementia and to quantify frailty to determine life expectancy and appropriate osteoporosis therapy. Patients are also referred to Geriatric Assessment Units and fall prevention programs. Patients are then contacted in the community at 3, 6,9,12 months by the FLS RN to follow up on osteoporosis therapy, and arrange other needed tests (i.e. bone mineral density, vitamin D) as needed. Information is sent to their family physician with all results. Prior to the patient's discharge from the FLS at one year, a final hand-over letter from the program will be provided outlining the plan of care for the patient. The FLS launched in June 2015 at the Misericordia hospital in Edmonton, Alberta (with plans to expand provincially). Currently 3 out of 4 hip fracture patients per week are being identified in the ED. Ninety-eight hip fracture patients have been identified post-surgery, with 71 patients eligible for enrollment in the program (five deceased patients). Sixty-six (50%) of those enrolled were discharged on osteoporosis medication compared to 8% prior to the program initiation. Seventeen (26%) of those were new medication starts. Of those not started, 7(11%) was patient choice. 11(31%) will be reassessed at 3 months for appropriate therapy. Nineteen (27%) of patients were referred to other inpatient or outpatient programs (i.e. falls, memory). Three month follow up calls have begun with patients for further data collection and a full 1 year qualitative and quantitative evaluation will be done. The implementation of an FLS with dedicated personnel to proactively manage and treat patients with appropriate investigations and interventions can close the care gap that exists in OP care. It also addresses gaps in senior care and provides appropriate referral to community geriatric programs, to improve quality of life and prevent future fractures

Background. Stress fracture of the acromium and scapular spine is a common complication following reverse total shoulder arthroplasty (RSA), with a reported incidence of 3.1%–11%. There is some evidence associating osteoporosis with increased risk of acromial stress fractures, but little else is known about the causes of acromial stress fractures after RSA. This study aims to define better preoperative factors, including demographics, comorbidities, and diagnoses, which predispose patients to postoperative acromial stress fractures. Methods. We retrospectively identified patients who underwent primary or revision RSA for any indication between January 2013 and December 2018 by two surgeons at two separate hospitals. Stress fractures of the acromion were identified on plain radiographs or computed tomography, when necessary. Patient demographics, comorbidities, and surgical indications were compared between patients with and without acromial stress fractures. Results. A total of 1,488 arthroplasties were identified and met the inclusion criteria. Of the study sample, 54 patients were diagnosed with a postoperative acromial stress fracture, an incidence of 3.6%. Patients in the stress fracture cohort were significantly more likely to have preoperative rotator cuff pathology (p<0.001), be of female gender (p<0.001), older (p=0.002), and osteoporotic (p<0.001; Table I). Thyroid disease (p=0.045) and inflammatory or rheumatoid arthritis (p=0.02) were also more frequent among patients with acromial stress fractures (Table I). No other comorbidities, including obesity (p=0.21) and diabetes (p=0.58), correlated significantly with postoperative acromial stress fracture (Table I). Conclusions. Old age, female gender, diagnosed osteoporosis, inflammatory arthritis, thyroid disease, and preoperative rotator cuff deficiency may all be risk factors for postoperative acromial stress fractures. Given that rotator cuff pathology is among the predominant indications for RSA, further research is required to determine the etiology and biomechanical basis for acromial stress fractures. For any figures or tables, please contact the authors directly

Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established. A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05. Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2. To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients

Introduction. Aseptic loosening is the main reason for total knee arthroplasty (TKA) failure, responsible for more than 25% of the revision procedures, with most of the problems occurring with the tibial component. While early loosening can be attributed to failure of primary fixation, late implant loosening is associated with loss of fixation secondary to bone resorption due to altered physiological load transfer to the tibial bone. Several attempts have been made to investigate these changes in bone load transfer in biomechanical simulations and bone remodeling analyses, which can be useful to provide information on the effect of patient, surgery, or design-related factors. On the other hand, these factors have also been investigated in clinical studies of radiographic changes of bone density following TKA. In this study we made an overview of the knowledge obtained from these clinical studies, which can be used to inform clinical decision making and implant design choices. Methods. A literature search was performed to identify clinical follow-up studies that monitored peri-prosthetic bone changes following TKA. Within these studies, effects of the following parameters on bone density changes were investigated: post-operative time, region of interest, alignment, body weight, systemic osteoporosis, implant design and cementation. Moreover, we investigated the effect of bone density loss on implant survival. Results. A total of 19 studies was included in this overview, with a number of included patients ranging from 12 to 7,760. Most studies used DEXA (n=16), while a few studies performed analyses on calibrated digital radiographs (n=2), or computed tomography (n=1). Postoperative follow-up varied from 9 months to 10 years. Studies consistently report the largest bone density reduction within the first postoperative year. Bone loss is mainly seen in the medial region. This has been attributed to the change in alignment following surgery, during which often the pre-operative varus knee is corrected to a more physiological alignment, resulting in a load shift towards the lateral compartment. Measurements in unoperated contralateral legs were performed in 3 cases, and two studies performed standardized DEXA measurements to provide information on systemic osteoporosis. While on the short term no changes were observed, significant negative correlations have been found between severity of osteoporosis and peri-prosthetic bone density. No clear effects of bodyweight and cementation on bone loss have been identified. Although some studies do find differences between implant types, the variation in the data makes it difficult to draw general conclusions from these findings. Several studies reported no effect of bone loss on implant migration. In another study, a medial collapse was associated with a medial increase in density, suggesting that altered loading and increased stresses are responsible for both bone formation and the overload leading to collapse. Discussion. There are important lessons to be learned from these clinical studies, although generally the large spread in the DEXA data restricts strong conclusions. There is a large variation in used ROI definitions, complicating direct comparisons. Finally, most studies report density changes of well-functioning reconstructions, since only very large studies are able to gather enough failed cases

Background. Stress fractures at tracker after computer navigated total knee replacement are rare. Periprosthetic fracture after Minimally Invasive Plate Osteosynthesis (MIPO) of stress fracture through femoral tracker is unique in orthopaedic literature. We are reporting this unique presentation of periprosthetic fractures after MIPO for stress fracture involving femoral pin site track in computer assisted total knee arthroplasty, treated by reconstruction nail (PFNA). Methods. A 75-year old female, who had computer navigated right total knee replacement, was admitted 6 weeks later with increasing pain over distal thigh for 3 weeks without trauma. Prior to onset of pain, she achieved a range of movements of 0–105 degrees. Perioperative radiographs did not suggest obvious osteoporosis, pre-existent benign or malignant lesion, or fracture. Radiographs demonstrated transverse fracture of distal third of femur through pin site track. We fixed the fracture with 11-hole combihole locking plate by MIPO technique. Eight weeks later, she was readmitted with periprosthetic fracture through screw hole at the tip of MIPO Plate and treated by Reconstruction Nail (PFNA), removal of locking screws and refixation of intermediate segment with unicortical locking screws. Then she was protected with plaster cylinder for 4 weeks and hinged brace for 2 months. Results. Retrograde nail for navigation pin site stress fracture entails intraarticular approach with attendant risks including scatches to prosthesis and joint infection. So we opted to fix by MIPO technique. Periprosthetic fracture at the top of MIPO merits fixation with antegrade nail in conjunction with conversion of screws in the proximal part of the plate to unicortical locking screws. Overlap of at least 3cms offers biomechanical superiority. She made an uneventful recovery and was started on osteoporosis treatment, pending DEXA scan. Conclusion. Reconstruction Nail (PFNA), refixation of intermediate segment with unicortical locking screws constitutes a logical management option for the unique periprosthetic fracture after MIPO of stress fracture involving femoral pin site track in computer assisted total knee replacement

Purpose. In 2010, the new clinical guideline of Osteoporosis Canada for the diagnosis of osteoporosis, clearly indicates that patients with high-risk of fracture are those that have already sustained a fracture (osteoporotic fracture). Until now, only 12% of the 3,400 fractures that we treat each year receive a treatment for osteoporosis. We are validating an evaluation protocol and a multidisciplinary systematic follow-up approach for osteoporosis. Patients are managed by a clinical nurse specialist. We are recruiting 543 patients with an osteoporotic fracture at Hal du Sacré-Coeur de Montréal. We aim to evaluate: 1) the incidence of a second osteoporotic fracture, 2) the initiation of a treatment and determine the compliance and adherence to treatment and 3) the evaluation of CTX-1 and Osteocalcin at Baseline, 6, 12,18 et 24 months (treatment efficacy) and 4) the functional outcome and quality of life post-fracture. Method. We've enrolled 153 subjects (men and women) over 40 years of age who were treated for an osteoporotic fracture at the orthopaedic clinic of Hal du Sacré-Coeur de Montréal. After starting a treatment protocol for osteoporosis, the subjects will be followed for a 24 months period at different time intervals. During these visits, they fill up functional outcome questionnaires, undergo physical exam, blood test, x rays and their compliance to treatment is evaluated. Results. Mean patients age was 65 y.o (+ 13). Two hundred seventeen patients were approached and 153 patients were enrolled (23 men and 130 women). Eleven patients refused to be part of the systematic follow up because they were satisfied with their family doctors osteoporosis management. Fifty-three were explained treatment and follow up and refused to participate. Thirteen patients (9%) dropped out after six months. One patient died. Twenty-one patients (13.7%) were already on bisphosphonates and 53 pts (34.6 %) had already sustained a fragility fracture. All patients were prescribed risedronate except three that were prescribed zoledronic acid or pamidronate for intolerance or contraindication to oral bisphosphonates. Up to now, we obtained 71% adherence and 91% persistence. After validation, 10% of the patients needed to be referred to a rheumatologist and 90% of the patients were managed by the clinical nurse specialist. Conclusion. Our multidisciplinary systematic follow up of osteoporotic fracture improved the osteoporosis treatment rate from 12 to 71 % in our orthopaedic surgery department. Clinical Nurse Specialists could represent the best approach to manage the underlying osteoporosis that leads to fragility fractures