Rate Of Fragility Fractures Research Articles

Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer

The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD) and lipid profile could be recommended for post-menopausal women candidate to AIs.

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis

The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 microg (TPTD20; N = 541), or teriparatide 40 microg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy.

Low Incidence of Anti-Osteoporosis Treatment After Hip Fracture

Following hip fracture, pharmacologic treatment can reduce the rate of subsequent fragility fractures. The objective of the present study was to assess the proportion of patients who are managed with bisphosphonates or selective estrogen-receptor modulators after hip fracture and to evaluate, among those managed with alendronate, the twelve-month compliance and persistence with treatment. Data were gathered from health insurance companies and were collected by AIM (Agence Intermutualiste) for the Belgian National Social Security Institute (INAMI). We selected all postmenopausal women who had been hospitalized for a hip fracture between April 2001 and June 2004 and had not been previously managed with bisphosphonates. Patients who had received alendronate treatment after the hip fracture were categorized according to their formulation use during the follow-up study (daily, weekly, daily followed by weekly, or weekly followed by weekly). Compliance at twelve months was quantified with use of the medication possession ratio (i.e., the number of days of alendronate supplied during the first year of treatment, divided by 365). Persistence with prescribed treatment was calculated as the number of days from the initial prescription to a lapse of more than five weeks after completion of the previous prescription refill. The cumulative treatment persistence rate was determined with use of Kaplan-Meier survival curves. A total of 23,146 patients who had sustained a hip fracture were identified. Of these patients, 6% received treatment during the study period: 4.6% received alendronate, 0.7% received risedronate, and 0.7% received raloxifene. Bisphosphonate treatment was dispensed to 2.6% and 3.6% of the patients within six months and one year after the occurrence of the hip fracture, respectively. Among women who received alendronate daily (n = 124) or weekly (n = 182) and were followed for at least one year after the hip fracture, the twelve-month mean medication possession ratio was 67% (65.9% in the daily group and 67.7% in the weekly group). The analysis of persistence with treatment included a total of 726 patients (142 in the daily group, 261 in the weekly group, and 323 in the switch group). At twelve months, the rate of persistence was 41% and the median duration of persistence was 40.3 weeks. The vast majority of patients who experience a hip fracture do not take anti-osteoporotic therapy after the fracture. Furthermore, among patients who begin alendronate treatment after the fracture, the adherence to treatment decreases over time and remains suboptimal.

Locking Plates

Locking plates are fracture fixation devices that allow the insertion of fixed-angle/angular-stable screws or pegs and do not require friction between the plate and bone. The clinical care impetus for the development of these plates has been a combination of factors, including the increasing survival of patients with high-energy injuries, aging Western European and North American populations with an increasing rate of fragility fractures, and dissatisfaction of patients and surgeons with the outcomes of treatment of specific periarticular fractures. Nonclinical factors likely include a push by industry for new technology and new markets as well as the general interest of the public in "minimally invasive" surgery.

Cortical Bone Histomorphometry of the Iliac Crest in Normal Black and White South African Adults

Fragility fracture rates in South African blacks (B) are lower than in whites (W). Since bone strength in many parts of the skeleton depends mainly on cortical bone, we examined iliac crest cortical bone from 97 B (49 male, 48 female) aged 22-80 and 111 W (60 male, 51 female) aged 21-84 histomorphometrically for differences between B and W and effects of age. B had thicker (P = 0.02) and less porous (P = 0.0007) cortices, fewer haversian (H) osteons (P < 0.0001), and greater endocortical (Ec) wall thickness (P < 0.0001). B also had thicker H (P = 0.0005) and Ec osteoid seams (P < 0.0001); greater Ec osteoid surface (P = 0.0005), Ec mineral apposition rate (P < 0.0001), and Ec bone formation rate (P = 0.038); and lower H (P = 0.0002) and Ec eroded surfaces (P = 0.029). Some of the differences were already present in subjects aged 21-30 years. Although cortical structure deteriorated with age in B and W, after age 40 Ec wall thickness declined only in W. Greater Ec mineral apposition and bone formation rates, i.e., greater osteoblast efficiency at the cellular and tissue levels, suggest better Ec bone preservation that may contribute to lower fragility fracture rates in B.

Osteoporosis in a population from medieval Norway

Modern populations from Norway and England differ in their experience of osteoporosis, the former showing lower bone mineral density (BMD) and a higher fragility fracture rate. The aim of the present work was to investigate whether this was also the case during the Middle Ages. Age-dependent loss of BMD in the proximal femur was assessed using dual X-ray absorptiometry (DXA) in male and female adult skeletons from a cemetery in the medieval town of Trondheim, Norway. Fracture prevalence was also investigated. Results were compared with those previously reported for a skeletal series from Wharram Percy, a deserted medieval village in England. Results indicate that peak BMD and patterns of age-related loss of BMD in the Norwegian and the English group were similar. Among females, the prevalence of osteoporotic fractures was greater in the Norwegian than in the English population. The BMD results suggest that differences in BMD between English and Norwegians are of recent origin, although given the fairly modest sample sizes, further work is needed to confirm this. Reasons for the greater prevalence of osteoporotic fractures in women in the Norwegian skeletal series are unclear, but the colder climate and greater frequency of hard surfaces may have meant that falls were more frequent, and when they occurred, were more likely to result in fractures than in the rural English group.

Epidemiology of hip fractures in 2002 in Rabat, Morocco.

Hip fracture has never been studied before, either in Morocco or in the adjacent countries of the south bank of the Mediterranean Sea. The aim of this study was to investigate the incidence rate of hip fracture in 2002 in Rabat Province, a large area in the northwest of The Kingdom of Morocco, by the use of register information and medical records collected from the five public hospitals of the region. The hip fracture data were restricted to cervical or trochanteric types. There was a total of 150 hip fractures (83 in women and 67 in men) in the over-50-year-old population in the Province of Rabat during 2002. The age-adjusted 1-year cumulative incidence of hip fracture was 52.1/100,000 [95% confidence interval (CI) 40.9-63.3/100,000] in women and 43.7/100,000 (95% CI 33.3-52.2/100,000) in men. The standardized incidence rate against the 1985 US population was 80.7/100,000 (95% CI 78.5-93.0/100,000) for women and 58.5/100,000 (95% CI 47.9-68.1/100,000) for men. The mean (standard deviation) age of patients with a hip fracture was 70.7 (9.4) years for women and 70.4 (10.0) years for men. The overall female-to-male ratio of hip fracture was 1.19 for age-adjusted hip fracture incidence and 1.30 for standardized incidence. A marked increase in incidence rate was found for both men and women with increasing age, becoming exponential after the age of 50 years. The mean age for hip fracture was 70.7 (9.4) years in women and 70.4 (10.0) years in men (P > 0.05). Women had a cervical-to-trochanteric ratio of 0.97 compared to men, at 1.03. The characteristics of hip fractures described in this study suggest that fragility fractures occur in North Africa, although substantially less frequently than in most European, North American and Asian countries but more frequently than sub-Saharan African countries, in agreement with the north-south gradient observed in the epidemiology of osteoporosis. The low incidence of hip fragility fracture rate is most likely the result of reduced longevity in Morocco.

Fewer bone histomorphometric abnormalities with intermittent than with continuous slow-release sodium fluoride therapy.

To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.