Decrease Fracture Risk Research Articles

Proximal femoral nailing for intertrochanteric fracture combined with contralateral femoral neck local osteo-enhancement procedure (LOEP) for severe osteoporotic bone loss: An original Italian case series.

Proximal femoral fractures in elderly women are a major cause of morbidity and mortality worldwide and a public health concern. Although pharmacological therapies have shown potential in improving bone mineral density (BMD) and decreasing fracture risk, the current research effort is focused on developing a procedure that can ensure both immediate and long-term efficacy. A minimally-invasive surgical approach, known as AGN1 local osteo-enhancement procedure (LOEP), has been recently developed to promote bone augmentation. The procedure implies the preparation of an enhancement site, a specific location where new bone is required within a local bony area weakened by osteoporotic bone loss, and the insertion of a triphasic, resorbable, calcium-based implant material. The results of this procedure have shown a significant and sustainable long-term increase in the proximal femur BMD and consequently in bone strength, thereby improving the femoral neck's resistance to compression and distraction forces that may result in fall-related fractures. A preliminary case series of ten women, suffering from intertrochanteric fracture and contralateral proximal femur severe osteoporotic bone loss, who underwent a combined procedure of proximal femoral nailing and AGN1 local osteo-enhancement procedure, has been developed over the course of a year of clinical and radiological data collection.

Associations between gut microbiota and incident fractures in the FINRISK cohort

The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87–0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85–0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07–1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85–0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.

A Comprehensive Narrative Review of the Impact of Pelvic Radiotherapy on Pelvic Bone Health: Pathophysiology, Early Diagnosis, and Prevention Strategies.

Radiotherapy is a commonly used modality in pelvic malignancies such as prostate, gastrointestinal, or gynecological, either as a primary treatment or an adjuvant post-surgery. Despite its positive impact on the prognosis of these patients, it was found in several studies that it contributes to insufficiency fractures in different sites of the pelvis, more commonly in the sacral ala. This is particularly true for elderly patients. There are several hypotheses on how radiotherapy affects bone health, as it destroys the bone matrix and causes obliterative vasculitis. Several imaging techniques, particularly magnetic resonance imaging (MRI), help detect the radiotherapy-induced fracture and distinguish it from metastases. Some modalities, such as intensity-modulated radiotherapy (IMRT) and brachytherapy, have decreased fracture risk by escaping the adjacent structures to the targeted organ. Pharmacological interventions such as amifostine and desferrioxamine are promising in terms of bone protection, which necessitates further studies to confirm their mechanism of action.

Impact of Vitamin D Status and Nutrition on the Occurrence of Long Bone Fractures Due to Falls in Elderly Subjects in the Vojvodina Region of Serbia.

Bone fractures are a significant public health issue among elderly subjects. This study examines the impact of diet and vitamin D status on the risk of long bone fractures due to falls in elderly subjects in Vojvodina, Serbia. Conducted at the University Clinical Center of Vojvodina in autumn/winter 2022-2023, the study included 210 subjects >65 years: 105 (F: 80/M: 15) with long bone fractures due to falls and 105 (F: 80/M: 15) controls. Groups were similar regarding age and BMI. Dietary intakes (by two 24-h recalls) and serum vitamin D levels were analyzed. The fracture group had a significantly lower median daily vitamin D intake (1.4 μg/day vs. 5.8 μg/day), intake of calcium, energy, proteins, fats, fibers, dairy products, eggs, fish, edible fats/oils, and a higher intake of sweets (p < 0.001 for all). Serum vitamin D levels were significantly lower in the fracture group (40.0 nmol/L vs. 76.0 nmol/L, p < 0.001). Logistic regression identified serum vitamin D as the most important protective factor against fractures, and ROC curve analysis indicated that serum vitamin D levels > 50.5 nmol/L decreased fracture risk. Nutritional improvements (increased intake of vitamin D and protein sources such as fish, eggs, and dairy), increased sun exposure, and routine vitamin D supplementation during winter are advised.

Effect of laparoscopic cholecystectomy on 25-hydroxyvitamin D levels and bone mineral density in post menopausal women

Background Laparoscopic cholecystectomy (LC) is the gold standard management for benign gallbladder diseases. It has been observed that there is alteration in vitamin D levels and bone mineral density after cholecystectomy due to altered enterohepatic circulation. With increase in average age expectancy of the population, low levels of vitamin D levels and osteoporosis after cholecystectomies might cause increased health care burden. Methods A prospective observational study was planned between 1 January 2022 and 30 June 2023 in the Department of General Surgery at PGIMER Chandigarh, a tertiary care hospital in north India. One hundred and three post-menopausal women who underwent LC and met the inclusion and exclusion criteria were included in the study. All participants underwent estimation of vitamin D and bone mineral density preoperatively and third-post operative month (POM). Results The mean age of the patients was 58.46 ± 7.44. Pain abdomen was present in 68(66%) patients, 18 had epigastric discomfort and 17 had dyspepsia. The mean levels of vitamin D decreased from 21.92 at the baseline to 20.12 at third POM (p < .001). There was a significant change in t score Femoral Neck (−1.12 vs −1.15, p < .001) and Lumbar spine L1–L4 − 1.98 vs −1.98 (p = .033). z-scores of the femoral neck were −0.34 vs −0.54 (p < .001) and of lumbar spine L1–L4 were −0.95 vs 1.02 (p < .001). The decrease in fracture risk for the femoral neck (p = .344) and the lumbar spine (p = .223) was not statistically significant. Conclusion There is a significant decrease in vitamin D and BMD levels after LC in post-menopausal females.

Skeletal Effect of Parathyroidectomy on Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis.

Parathyroidectomy (PTX) is recommended for curing primary hyperparathyroidism (PHPT), although uncertainty remains regarding the extent of fracture risk reduction following surgery. This work aimed to compare fracture risk and bone mineral density (BMD) changes in patients with PHPT undergoing PTX vs observation (OBS). We systematically searched PubMed, Embase, and the Cochrane Library until September 2022, including randomized controlled trials (RCTs) and cohort studies, and reviewed citations from previous reviews. Among 1260 initial records, 48 eligible articles from 35 studies (5 RCTs; 30 cohorts) included PHPT patients receiving PTX or OBS interventions with reported fracture events at any site, including the hip, spine, or forearm, and/or BMD changes at each location. Data extraction followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines by 2 independent reviewers. In 238 188 PHPT patients (PTX: 73 778 vs OBS: 164 410), PTX significantly reduced fractures at any site (relative risk [RR], 0.80; 95% CI, 0.74-0.86) compared to OBS. In 237 217 patients (PTX: 73 458 vs OBS: 163 759), the risk of hip fractures decreased (RR, 0.63; 95% CI, 0.52-0.76). No reduction in forearm and vertebral fractures was observed in 3574 and 3795 patients, respectively. The annual percentage BMD changes from baseline were higher in the PTX group: femoral neck, 1.91% (95% CI, 1.14-2.68); hip, 1.75% (95% CI, 0.58-2.92); radius, 1.75% (95% CI, 0.31-3.18); spine, 2.13% (95% CI, 1.16-3.10). PTX significantly reduced overall and hip fracture risks in PHPT patients. Despite minimal BMD increase, the substantial decrease in fracture risk suggests additional benefits of PTX beyond mineral content enhancement.

The risk of bone fractures in dementia patients receiving acetylcholinesterase inhibitors: a meta-analysis.

The authors aimed to conduct a meta-analysis to determine if acetylcholinesterase inhibitors may pose a direct threat, increasing the incidence of fractures in dementia patients. PubMed, Scopus, and Cochrane Library were searched. Inclusion criteria were any original studies that demonstrated the link between acetylcholinesterase inhibitors and the incidence of fracture in patients with dementia. RevMan(5.4) was used. Seven observational studies were included. The total number of patients included in the acetylcholinesterase inhibitors group is 274332 and 290347 in the control group. The pooled analysis showed that the risk of bone fracture was not statistically different between dementia patients who received acetylcholinesterase inhibitors and those who did not receive them (odds ratio=1.44, CI 0.95, 2.19, P=0.09). Subgroup analysis showed no statistically significant difference between dementia patients who took acetylcholinesterase inhibitors, and those who didn't take acetylcholinesterase inhibitors in those more than or equal to 80 years old and those less than 80 years old (P=0.44) and (P=0.34) respectively. However, our results showed a statistically significant association between dementia patients who received acetylcholinesterase inhibitors and decreased fracture risk in those receiving the treatment for more than or less than 2 years (risk ratio=0.48, CI= 0.45, 0.51, P<0.00001) and (risk ratio=0.84, CI 0.70, 0.99, P=0.04), respectively. Our study revealed no role for acetylcholinesterase inhibitors in increasing the risk of fracture compared with controls. Hence, based on our analysis, they might have a protective role against fracture when used for long periods considering their positive action on bone growth and development. Therefore, Acetylcholinesterase inhibitors could be considered a safe option for improving cognitive functions in elderly demented patients without carrying any additional risks.

Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?

BackgroundPrevious studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort.MethodsIn total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks’ gestation) and/or 28–32 weeks’ gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002–2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample.ResultsData were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24).ConclusionsWhile our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.

Femoral neck width genetic risk score is a novel independent risk factor for hip fractures.

Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29-1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30-1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n= 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05-1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06-1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction.

Indices of sarcopenic obesity are important predictors of finite element analysis-derived bone strength in older adults with obesity.

The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT). One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement. Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2=0.301 to 0.448, HGS: R 2=0.346 to 0.472, FM%: R 2=0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05). These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

Evaluation of bone mineral density, microarchitecture, and detection of fractures on young patients living with human immunodeficiency virus: when and how to screen?

People living with the human immunodeficiency virus (PLWH) developed higher life expectancy along with chronic bone disease over the past years. Our purpose is to evaluate bone mineral density, bone microarchitecture and fractures in young PLWH and understand the disease's contribution to bone derangements and fracture risk. Eighty-one HIV-infected and 54 control young (20-50 years) male and female subjects were enrolled in this study. Methods for patient evaluation included DXA-VFA (dual energy X-rays and vertebral fracture assessment), HR-pQCT (high resolution peripheral quantitative computed tomography), biochemistry and FRAX. Fifty participants from each group completed all exams. Median age was 40 (25-49) vs. 36.5 (22-50) for the HIV and control groups, respectively (p 0.120). Ethnicity, body mass index, serum phosphorus, 25-hydroxyvitamin D, PTH and CTX were similar between groups, although ALP and OC suggested higher bone turnover in PLWH. VFA identified morphometric vertebral fractures in 12% of PLWH. PLWH had lower values for lumbar spine areal BMD and Z score, volumetric BMD, trabecular bone fraction (BV/TV) and trabecular number measured at the distal tibia by HR-pQCT; as a consequence, trabecular separation and heterogeneity were higher (all p < 0.05). The FRAX-estimated risk for hip and major osteoporotic fractures was statistically higher in PLWH (p < 0.001). Our results confirm severe bone impairment and fractures associated with HIV in young patients. Thus, we developed a screening protocol for young PLWH to detect bone fragility, reduce skeletal disease progression and morbimortality, decrease fracture risk, and increase quality of life.

The influence of growth hormone deficiency on bone health and metabolisms.

Growth hormone (GH) is a key peptide hormone in the regulation of bone metabolism, through its systemic and paracrine action mediated directly as well as by insulin-like growth factor-1 (IGF-1). Growth hormone exerts pleiotropic effects leading to an increase in linear bone growth, accumulation of bone mineral content and preservation of peak bone mass. Furthermore, it influences protein, lipid, and carbohydrate metabolism.Growth hormone deficiency (GHD) causes a low bone turnover rate leading to reduced bone mineral density (BMD) and increased bone fragility. The results of GH insufficiency are the most pronounced among children as it negatively affects longitudinal bone growth, causing short stature and in adolescents, in whom it hinders the acquisition of peak bone mass. Most studies show that treatment with recombinant human growth hormone (rhGH) in GHD patients could improve BMD and decrease fracture risk. This review aims to summarize the pathophysiology, clinical picture and management of bone complications observed in GHD.

A Scoping Review to Assess Risk of Fracture Associated with Anxiolytic Medications.

Recent research has focused on evaluating the impact of pharmalogical sources on fracture risk. The purpose of this study was to review the literature on anxiolytic medications that may be associated with an increased risk of fracture. A search was conducted in MEDLINE and Embase databases to identify primary clinical studies of patients who sustained a fracture while prescribed anxiolytic medications and were published prior to July 2021. Anxiolytics defined by ATC Class N05B, beta blockers, and zolpidem were included. The search terms consisted of variations of the following: ("Psychotropic Drugs" or MeSH terms) AND ("Fracture" or MeSH terms). Of 3,213 studies, 13 (0.4%) met inclusion criteria and were evaluated. Fractures associated with benzodiazepine were reported in 12 of 13 studies; the highest risk occurred in patients aged 60 years and older (RR=2.29, 95% CI (1.48-4.40)). The ATC Class N05B showed an increased fracture risk for those ≤ 55 years of age that differed by sex: for men (RR=5.42, 95% CI(4.86-6.05)) and for women (RR=3.33, 95% CI (3.03-3.66)). Zolpidem also showed an increase fracture risk (RR=2.29, 95% CI(1.48-3.56)), but only during the first four weeks of treatment. A relative risk of 0.77, 95% CI(0.72-0.83) was observed for beta blockers. Fractures are a mainstay of traumatic injuries and are accompanied by economical, physiological, and psychological hardship. With proper assessment and prophylactic measures, fracture risk can be reduced dramatically. Anxiolytic medications have been described widely to increase fracture risk, such as benzodiazepines in 60+ year old patients, and ATC Class N05B anxiolytics increased fracture risk in 55+ year old men and in 55+ year old women. Yet, some studies showed that at low doses, nitrazepam lowered fracture risk. Other anxiolytic medications, such as zolpidem and beta blockers, also showed a decrease in fracture risk. Ultimately, this scoping review helped to illuminate the inconsistency of anxiolytic fracture risk assessment while simultaneously illustrating the necessary steps to guide future research.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. 241 consecutive women (median age 58years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24months of follow-up. During the study period, 139 women (57.7%) received denosumab 60mg every 6months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

A narrative review of the pharmaceutical management of osteoporosis.

Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can be divided into categories based on its etiology: senile, post-menopausal, and secondary osteoporosis. Specific prevention measures and treatments exist for targeting bone loss. Here we review and summarize the literature regarding the presentation of osteoporosis and discuss pharmaceutical therapies. PubMed and Google Scholar were searched for articles published in English between 1980 and 2021. Search terms combined "senile osteoporosis", "osteoporosis treatment", "osteoporosis", "bisphosphonates", "denosumab", types of hormone therapy, and other relevant keywords used in various combinations. Osteoporosis affects millions but often goes undiagnosed until a pathologic fracture. Dual-energy X-ray absorptiometry (DEXA) scans evaluate bone mineral density (BMD) and are a diagnostic tool for osteoporosis. Adults over the age of 65, post-menopausal women, and those with risk factors such as previous fractures are recommended to receive DEXA scans every one to two years. Bisphosphonates, denosumab, and hormonal therapies are among the most common pharmacologic treatments for osteoporosis. Daily, orally administered bisphosphonates are the first-line therapy for osteoporosis given their efficacy in decreasing fracture risk and favorable safety profile. Denosumab is an alternative that is administered subcutaneously every six months and may be given as initial therapy to select patients. Hormonal therapies are used if patients cannot tolerate bisphosphonates or denosumab or are refractory to these medications. Preventative measures for osteoporosis include tailored exercise and sufficient intake of calcium and vitamin D via diet or supplementation.

Bones of contention: Predicting and preventing fractures in patients receiving peritoneal dialysis.

Low bone density is common among those individuals receiving peritoneal dialysis. While cross-sectional studies support an association between low bone mineral density (BMD) and prevalent fracture, relying on bone density alone, particularly at the lumbar spine and in those with high degrees of hyperparathyroidism may underestimate fracture risk. Commonly used risk calculators in the general population have been shown to perform reasonably well in those receiving dialysis although they do not include any risk factors for high turnover bone disease that may play a role in increased fracture risk. The best options for decreasing fracture risk in patients receiving peritoneal dialysis are unclear. The evidence for bisphosphonates is limited to small studies of BMD, and concerns about drug accumulation have limited their use. Denosumab is more commonly used and has some evidence for improvement in BMD but carries with it a high risk of hypocalcaemia requiring rigorous prophylaxis. More research is needed to explore practical methods to identify those at risk of fracture and determine the efficacy of antiresorptive and anabolic therapies to decrease this risk.

Conventional androgen deprivation therapy is associated with an increased risk of fracture in advanced prostate cancer, a nationwide population-based study.

Androgen deprivation therapy (ADT) is the standard of care in advanced prostate cancer. We conducted a Taiwan National Health Insurance Research Database (NHIRD) study to evaluate the association between ADT and fracture risk in patient with prostate cancer in Taiwan. Between 2001 and 2008, data from the Taiwan NHIRD was collected. We separated newly diagnosed prostate cancer patients into four groups: the injection of gonadotropin-releasing hormone agonists and antagonists group, the orchiectomy group, the oral antiandorgens group and the radical prostatectomy only group. A non-cancer matched control group was also assigned for comparison. T tests, chi-squared tests, multivariate Cox proportional hazard regression were performed. A subsequent fracture event was defined according to the appropriate diagnosis codes (ICD9-CM 800-829) with hospitalization. Patients with fracture before their diagnosis with prostate cancer were excluded. Overall, 22517 newly diagnosed patients with prostate cancer were enrolled in the study. After exclusion criteria were applied, 13321 patients were separated into the injection group (5020 subjects), the orchiectomy group (1193 subjects), the oral group (6059 subjects) and the radical prostatectomy only group (1049 subjects). The mean age of the overall study population was 74.4 years. Multi-variant analysis disclosed a significantly increased risk of fracture in the injection group, the orchiectomy group, and the oral group (hazard ratio [HR] = 1.55, 95%, confidence interval [CI] 1.36 to 1.76, p<0.001, HR = 1.95, 95%, CI 1.61 to 2.37, p<0.001, HR = 1.37, 95%, CI 1.22 to 1.53, p<0.001, respectively). In contrast, a significantly decreased fracture risk was noted in the radical prostatectomy only group (HR = 0.51, 95%, CI 0.35 to 0.74, p = 0.001). Patients receiving osteoporosis medication had a significantly decreased fracture risk (HR = 0.26, 95%, CI 0.19-0.37, p<0.001). ADT is associated with an increased risk of fracture. For patients receiving long-term prostate cancer castration therapy, doctors should always keep this complication in mind and arrange proper monitoring and provide timely osteoporosis medication.

Bone turnover markers to monitor oral bisphosphonate therapy.

Bisphosphonates are widely used as first-line therapy to slow bone loss and decrease fracture risk in postmenopausal women with osteoporosis. Nonadherence to oral bisphosphonates diminishes the benefit of reduced bone loss and fracture risk of these medications. Strategies to enhance osteoporosis monitoring and adherence to therapy are crucial to improve outcomes. Dual-energy x-ray absorptiometry (DXA) is the gold standard for monitoring bone mineral density but is slow to detect change after initiation of oral bisphosphonate therapy. Bone turnover markers (BTMs) are by-products released during bone remodeling and are measurable in blood and urine. We review how the rapid change in BTMs can be a useful short-term tool to monitor the effectiveness of oral bisphosphonate therapy, which may ultimately improve adherence to therapy and outcomes.

The why and how of sequential and combination therapy in osteoporosis. A review of the current evidence.

It is now well recognized that over the lifetime of a patient with osteoporosis, more than one medication will be needed to treat the disease and to decrease fracture risk. Though current gaps in osteoporosis therapy can be potentially mitigated with sequential and combination regimens, how to move seamlessly amongst the multiple treatments currently available for osteoporosis for sustained efficacy is still unclear. Data from recent studies show that an anabolic agent such as teriparatide or romosozumab followed by an antiresorptive affords maximal gain in BMD and possibly better and earlier fracture risk reduction compared to a regimen which follows the opposite sequence. Sequentially moving to a bisphosphonate such as alendronate from an anabolic agent such as abaloparatide has also been shown to preserve the fracture reduction benefits seen with the latter. This sequence of an anabolic agent followed by an antiresorptive should especially be considered in the high-risk patient with imminent fracture risk to rapidly reduce the risk of subsequent fractures. The data surrounding optimum timing of initiation of bisphosphonate therapy following denosumab discontinuation is still unclear. Though data suggests that combining a bisphosphonate with teriparatide does not provide substantial BMD gains compared to monotherapy, the concomitant administration of denosumab with teriparatide has been shown to significantly increase areal BMD as well as to increase volumetric BMD and estimated bone strength. This narrative review explores the available evidence regarding the various sequential and combination therapy approaches and the potential role they could play in better managing osteoporosis.

Bisphosphonates-what’s new?

Bisphosphonates are chemical-related to pyrophosphate. The oxygen atom in pyrophosphate is substituted by a carbon atom in these compounds, resulting in a P-C-P bond. They are potent antiresorptive medicines because they have a strong inhibitory effect on osteoclasts. It lowers fracture risk by reducing bone turnover, increasing bone mineral density, and decreasing fracture risk in the lumbar spine and hip. Bisphosphonates are strongly attracted to bone surfaces, where they accumulate, primarily at remodeling sites. They are rarely associated with systemic side effects due to their selectivity in action. Irritation of the upper gastrointestinal tract is the most common side effect. A strong third-generation bisphosphonate, zoledronate, is currently approved to treat postmenopausal-induced osteoporosis. This review mainly focuses on the mechanism of action, therapeutic uses, and its adverse effects.