Risk Factors For New Fractures Research Articles

The Relationship Between Fracture and Mortality in a Chinese Maintenance Hemodialysis Patients Cohort.

Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear. A total of 182 maintenance hemodialysis patients were enrolled in the study. The relationship between fracture and poor prognosis (cardiovascular events, stroke, malignancy and 5-year all-cause mortality) were analyzed. 21 of 182 patients had a history of fracture at the time of enrollment. 26 patients had a new fracture after enrollment. A total of 57 fractures occurred in 47 patients, the most common fracture site was the rib. Patients with fracture group had a higher proportion of elderly and female, higher serum phosphorus and B-type natriuretic peptide and lower hemoglobin, albumin, and potassium compared with those without fracture. Age (OR=3.809, 95% CI: 1.064-8.966, p=0.038), hemoglobin (OR=0.961, 95% CI: 0.925-0.997, p=0.035), and serum phosphorus (OR=3.325, 95% CI:1.104-10.019, p=0.033) were the independent risk factors of new fractures in MHD patients. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture (p<0.05). But there was no significant difference in the incidence of acute myocardial infarction or stroke. 25.8% of maintenance hemodialysis patients had at least one fracture, with rib fractures accounting for the highest proportion. Age, hemoglobin and serum phosphorus were the independent risk factors of new fractures. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture, but there was no significant difference in the incidence of acute myocardial infarction and stroke.

Vitamin D deficiency is a risk factor for new fractures in Japanese postmenopausal women with rheumatoid arthritis: results from the IORRA cohort study.

Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures. Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50years (mean age, 65.9years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture. New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02‒2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14‒2.69]; p = 0.0109). Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures.

03:27 PM Abstract No. 299 Percutaneous vertebroplasty is not a risk factor for new fractures and protects against further height loss: results from VERTOS IV

Percutaneous vertebroplasty (PV) is an alternative option to treat pain after an osteoporotic vertebral compression fracture (OVCF). Controversy exists as to whether PV increases the risk for new OVCFs or prevents further vertebral height loss in treated levels. We assessed both during one year follow-up in patients with acute OVCF randomised to PV or a sham procedure. VERTOS IV is a prospective multicentre randomised controlled trial (RCT) comparing PV with sham therapy in 180 patients. New OVCFs and further vertebral height loss were assessed at 3, 6 and 12 months. After a median follow-up of 12 months (interquartile range (IQR)= 12-12) 31 new fractures were reported in 15 patients from the PV group and 28 new fractures in 19 patients from the sham group. The difference in incidence was not significant (F(1,522)=0.277, p=0.60). There was no higher fracture risk for adjacent versus distant vertebrae. After sham procedure, further height loss of treated vertebrae occurred more frequently (7 patients in the PV group and 36 in the sham group- (F(1,1222)=12, p < .001) and was more severe (p < .001) than after PV. PV does not increase the risk of OVCFs in the first year after cementation when compared to a sham procedure. The risk of further vertebral height loss is significantly higher after sham intervention, i.e., cementation protects against progressive vertebral body collapse.

Impact of Cement Placement and Leakage in Osteoporotic Vertebral Compression Fractures Followed by Percutaneous Vertebroplasty

Retrospective study. Assessment of the impact of cement placement and leakage in osteoporotic vertebral compression fractures (OVCFs) followed by percutaneous vertebroplasty (PVP) on patient pain relief and new vertebral fracture occurrence. Previous studies have not specifically addressed cement placement in the context of pain outcomes and subsequent vertebral fracture. We included a total of 192 patients who underwent PVP for OVCFs. We assessed imaging data, and patients rated their pain over a 24-month period. The patients were divided into 3 groups based on image analysis: group 1 [31 cases: 5 thoracic, 15 thoracolumbar (TL) junction, 11 lumbar] included patients with no cement extension to the endplate(s), group 2 (121 cases: 19 thoracic, 64 TL junction, 38 lumbar) was comprised of patients with cement extension to the endplate(s) but no leakage into the disk space, and group 3 (40 cases: 8 thoracic, 21 TL junction, 11 lumbar) included patients with cement extension to the endplate(s) and leakage into the disk space(s). We assessed the correlation between cement location and pain ratings and changes in pain scores, as well as the proportions of new fracture. Postprocedure pain numeric scores and changes in pain scores were similar among the 3 groups (P>0.05). Cement location did not significantly correlate with pain ratings or changes in pain scores for any follow-up points. There was no significant difference in new adjacent fracture rate among the groups (P>0.05). Neither extension of cement to the endplate nor cement leakage into the disk space had a significant impact on postprocedural pain. Furthermore, intradisk cement leakage was not a risk factor for new fracture after PVP in patients with OVCF. However, lower fill volumes should be used to lessen the risk of leakage.

Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian prospective cohort study.

Rheumatoid arthritis (RA) patients have high risk for osteoporosis and fracture. We aimed to identify the incidence rate and risk factors of fractures in Asian RA patients. A total of 3557 RA patients in the KORean Observational study Network for Arthritis (KORONA) were included and observed over a mean follow-up of 18months. A fracture was assessed as total, major, or minor fractures; major fracture was defined as a vertebral or hip fracture, and the other fractures were classified as minor fractures. The standardized incidence ratio (SIR) of fracture in RA patients was calculated compared with general population, and possible risk factors for fractures were explored using multivariable logistic regression analyses. A total of 194 patients with 215 fractures were observed, and the SIR of the total fracture in RA patients was 2.2 [95% confidence interval (CI) 1.9-2.6]. The SIRs of major and minor fractures were 1.5 (CI 1.1-2.0) and 3.0 (CI 2.5-3.7), respectively. Advanced age [odds ratio (OR) 1.03, CI 1.02-1.05, p<0.01] and having history of prior fracture (OR 2.17, CI 1.54-3.08, p<0.01) were risk factors for total fractures. In addition, higher HAQ increased fracture risk (OR 2.02, CI 1.05-3.89, p=0.04), whereas the use of bisphosphonate showed protective effect for future fractures (OR 0.34, CI 0.14-0.87, p=0.02) in patients with osteoporosis. RA patients had a 2.2-fold increased risk of fractures as compared with general population. In Asian RA patients, advanced age and history of prior fracture were the most important risk factors for new fractures.

Diagnosis of vertebral fractures using a low-dose biplanar imaging system.

Vertebral fractures (VFs) are independent risk factors for new fractures. However, spine radiographs cannot be used as a screening method. EOS® has a good diagnostic value for the diagnosis of VF with a better legibility of upper thoracic spine and a higher concordance between readers compared to vertebral fracture assessment (VFA). Vertebral fractures (VFs) are risk factors for new fractures. However, spine radiographs cannot be used as a screening method for both cost and radiation concerns. EOS® X-ray imaging system which allows the acquisition of biplane images in an upright weight-bearing position with low radiation dose was used. The objective of this study was to compare EOS® to VFA for the diagnosis of VF. We conducted a cross-sectional study in subjects aged above 50 years with indication for spine imaging. EOS® and VFA of the spine were performed the same day. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), and the interobserver precision of EOS® were compared to VFA for the diagnosis of VF. Two hundred patients (mean age 66.2 years) were included. At the vertebral level, 2.4 and 3.6 % of vertebrae were not legible using EOS® and VFA, respectively (p = 0.0007). The legibility of spine was significantly affected by scoliosis (odds ratio (OR) = 2.8, p < 0.0001, for EOS®, and OR = 1.8, p = 0.0041, for VFA). Sixty-six patients (33.0 %) and 69 (34.5 %) had at least one VF using VFA and EOS®, respectively. At patient level, Se, Sp, and NPV for the diagnosis of VF of EOS® were 79.7, 91.6, and 99 %, respectively. Concordance between both observers was very good for EOS® (kappa-score = 0.89), higher than for VFA (κ = 0.67). This study shows that EOS® has a good diagnostic value for the diagnosis of VF with a better legibility of upper thoracic spine and a higher concordance between readers compared to VFA.

Clinical and Radiographic Results of Kyphoplasty with Mid-Term Follow-Up

The goal of our retrospective case series is to understand better the demographics and outcomes of kyphoplasty in improving pain in insufficiency fractures that are non-responsive to conservative treatment, identify risk factors for recurrence of back pain due to new fractures or not, discern and understand the timing for symptom improvement after the procedure, and correlate the amount of vertebral height correction with clinical improvement. We hypothesized that kyphoplasty would be effective for pain management in vertebral compression fractures that have been refractory to clinical management. Eighty-one patients underwent kyphoplasty and were followed at two, four, and nine weeks and at one year. Demographics, clinical and radiographic outcomes, and risk factors for new fractures and other complications were analyzed. Maximal improvement in the VAS was seen at two weeks in 90% of our patients and at nine weeks 100% reached maximal improvement. At one-year follow up, recurrent or new onset back pain was noted in 27% of patients, while only 24% of had new vertebral fractures. Fractures at the adjacent level accounted for 50% of the new onset insufficiency vertebral fractures. Approximately 50% of patients had passed away or were not reachable at one year. Also, 50% of our osteoporotic compression fractures happened at the upper lumbar spine. Female sex was the only significant risk factor for subsequent new onset back pain. Male sex and lumbar fractures responded worse to the kyphoplasty treatment. Finally, the amount of radiographic reduction did not correlate with clinical outcomes. From the data analyzed from this case series, we found that kyphoplasty provides a safe and effective treatment for pain in patients with vertebral compression fractures.

Prone position in balloon kyphoplasty leads to no secondary vertebral compression fractures in osteoporotic spine - a MRI study.

Purpose: Vertebral compression fractures are the most common fractures in the elderly. Long lasting pain and deformity is responsible for consecutive impairment with markedly reduced life quality, increased morbidity and mortality. The beneficial effects of balloon kyphoplasty are verified in many studies. Subsequent fracture risk is not finally clarified, cement related risks and deformity related risks are discussed. There is less knowledge about the risk of bone marrow edema and new fractures during balloon kyphoplasty procedure. The goal of this study is to examine, if prone position during kyphoplasty is an independent risk factor for new fractures in the osteoporotic spine. Methods: Consecutive MRI study of 20 patients with fresh, non-traumatic thoracolumbar vertebral compression fractures and balloon kyphoplasty treatment. MRI Scans of the thoracolumbar spine were obtained after surgery, before patients have been mobilized. Specific MRI changes like new bone marrow edema, signal intensity changes in adjacent and remote segments and new fractures were assessed by specialized neuro-radiologist. Results: 20 MR images were examined within 48 hours after balloon kyphoplasty procedure. 85% did not show bone marrow edema extent changes after kyphoplasty. We found minor increase of bone marrow edema within the augmented vertebral body in 3 cases. We did not find any new bone marrow edema and no new fractures in adjacent and remote segments after balloon kyphoplasty treatment.Conclusion: Prone position leads to no new bone marrow edema and no new fractures in the osteoporotic spine. Accordingly, prone position has no risk for adjacent level fractures in osteoporotic spines.

Prevention of incident fractures in patients with prevalent fragility fractures: Current and future approaches.

Fragility fractures are a significant, independent risk factor for new fractures, but treatment uptake in subjects with prevalent fractures is disappointing. We addressed the question of the efficacy of pharmacological interventions in reducing the risk of incident fractures in patients with prevalent fragility fractures. For this, we reviewed randomised controlled trials (RCTs), pre-planned and post-hoc analyses of RCTs of approved agents for the treatment of osteoporosis. Results showed that a number of agents decrease the risk of incident vertebral and nonvertebral fractures in subjects with prevalent vertebral fractures, justifying the recommendation of treating such patients independently of the level of bone mineral density (BMD). By contrast, the evidence of antifracture efficacy of these agents in patients with prevalent nonvertebral fractures is limited. Advances in our understanding of the regulation of bone metabolism at the molecular level have identified targets for the development of new therapeutics for osteoporosis, some of which are currently in phase 3 clinical development.

Exposure to Proton Pump Inhibitors is a Risk Factor for New Fractures in Hepatitis C Patients Following IFN/Ribavirin Therapy Irrespective of Virological Response

Purpose: Overall incidence of bone fractures among HCV positive patients is higher in those who receive proton pump inhibitors (PPI) than in those who do not receive PPI. The purpose of this study is to determine whether the increased bone fracture incidence in hepatitis C patients associated with PPI is dependent upon viral clearance. Methods: A retrospective cohort study of the incidence of bone fractures after treatment with interferon/ribavirin (IFN/RIB) based therapy treated between 1/1999 and 1/2011 in 365 HCV antibody positive veterans was performed. The primary study endpoints were the number of bone fractures after therapy in HCV patients with a response (R), defined as an SVR or end of treatment response (ETR) or those with NR (defined as nonresponder or relapser). For both HCV groups (R and NR), the beginning and final date of the bone fracture observation period was defined as 6 months after IFN/RIB therapy and the study end date, respectively. Body mass index (BMI), calcium levels, ethnicity, tobacco, alcohol and PPI use were collected. Statistical differences in fracture incidence between groups were determined by Mann Whitney U and multivariable regression analysis. Results: Our cohort was 92.3% male, 70% W, 26% AA and 2% H with a mean age of 57.7 yrs. Response occurred in 44% of HCV patients, with significantly more AA in NR than R (34% vs 13%) but with no differences between groups in BMI, calcium levels, gender, alcohol, and PPI use. Among the study population with complete data analyzed (n=342), similar number of fractures were noted after IFN/RIB therapy in NR (n=7) and R (n=6) groups. After adjusting for ethnicity, gender, BMI, alcohol, tobacco and PPI use, there was no difference in new bone fracture incidence between R and NR in patients with chronic HCV. Of interest, more PPI users had fractures post IFN/Rib therapy than non PPI users (p = 0.003). Conclusion: In patients with chronic HCV, SVR did not confer a decreased risk of new bone fractures. Importantly, PPI were a risk factor for new fractures in Hepatitis C patients after IFN/Ribavirin therapy,irrespective of Hepatitis C viral clearance.

Defining High Risk of Osteoporotic Fracture

: There is no universally accepted definition for patients at high risk of osteoporotic fracture. : This study aimed to survey Spanish rheumatologists; to obtain opinions about risk factors, and an acceptable definition for patients at high risk of osteoporotic fracture; and to compare daily practice patterns with current osteoporosis guidelines. : A total of 174 rheumatologists from throughout Spain completed an online survey about various risk factors for fragility fracture and about the management of patients with osteoporosis in clinical practice. Results were reviewed by a coordinating committee of osteoporosis experts and were compared with published national and international guideline recommendations. : Almost all rheumatologists who completed the survey (99%) consider that a group of patients exists with a high risk of osteoporotic fracture and that this group should be managed appropriately. Previous fracture is considered the most important risk factor, particularly in cases of multiple fracture, severe vertebral fracture, hip fracture, or fracture despite osteoporosis treatment. However, in osteoporosis guidelines, age, bone mineral density, and previous fragility fracture are the most important risk factors for new fracture. Furthermore, Spanish rheumatologists tend to treat patients at high risk of fracture with anabolic therapy (e.g., teriparatide), whereas guidelines make no such recommendation. : In osteoporosis, a large gap exists between implementation of guideline recommendations and actual clinical practice; this may be due, in part, to heterogeneity among existing guidelines. Thus, inclusion in guidelines of a practical definition of high risk of osteoporotic fracture may provide significant opportunities to improve patient care and prevent future fragility fractures. :

Combined Vertebral Fracture Assessment and Bone Mineral Density Measurement: A Patient-friendly New Tool with an Important Impact on the Canadian Risk Fracture Classification

Purpose Vertebral fractures often go unnoticed, while they constitute a significant risk factor for new fractures, independent of the bone density. Vertebral Fracture Assessment (VFA) is a new feature on DXA bone densitometry equipment. Our purpose was to determine the added value of VFA and its impact on the Canadian fracture risk classification using data from a Dutch academic cohort. Methods All 958 consecutive patients (64% female, mean age 53 [20–94], mean weight 75 kg [32–150]) who underwent BMD measurement at the University Medical Center Groningen, The Netherlands also underwent VFA in the same session. Results The prevalence of vertebral fractures was 26%. In 68% of these patients this fracture was unknown. The severity was “mild” (20%–25% height loss) in 43%, “moderate” (25%–35%) in 44% and “severe” (>35% height loss) in 13%. Even after excluding mild fractures, the prevalence of vertebral fractures was 17%. In the 28% with normal BMD the vertebral fracture prevalence was still 18%, in the 43% with osteopenia 23%, and in the 29% with osteoporosis 36%. The Canadian risk classification was “low fracture risk” in 68%, “moderate” in 19%, and “high” in 13%. Adding VFA altered the classification in 20% of the patients, to become 54%, 27%, and 19%, respectively. Conclusions VFA added to BMD is a patient friendly diagnostic tool with a high diagnostic yield, as it detected unknown vertebral fractures and altered diagnostic classification in approximately 1 out of every 5 patients. These results suggest that BMD plus VFA may become the new standard in osteoporosis testing.

Factores predictivos de nueva fractura tras vertebroplastia

Purpose To evaluate the risk factors of new fractures after vertebroplasty (VP). Patients and method Prospective, non-randomized study including patients with acute osteoporotic fractures treated with VP. Baseline visit included clinical and densitometric data. At 30, 90 and 180 days, changes in clinical data and side effects (cement leakage and new fractures) were recorded. To establish the predictive factors of a new fracture, differences between the group of patients with new fractures (R1) and those without fractures (R0) were evaluated. Results Vertebroplasty was performed in 43 patients (82 vertebrae). Cement leakage into a disc appeared in 11 cases (11,5%) and 12 new fractures occurred in 9 patients. No statistical differences were detected between groups R1 and R0 in the following variables: sex, age, vitamin D levels, T-score, kyphosis angle, primary/secondary osteoporosis, preexisting fractures, number of treated vertebrae and amount of cement injected. A positive, statistical significant correlation, was established between cement leakage into a disk and incidence of adjacent new fractures (p<0.001). Conclusions Cement leakage into a disc increases the risk of adjacent new fractures after vertebroplasty.

New Vertebral Fracture After Vertebroplasty

Because the complications of vertebroplasty are serious and can include new fracture, we retrospectively evaluated potential risk factors for new fracture after vertebroplasty. Our hypothesis is that thoracolumbar vertebrae adjacent to a vertebroplasty site have a higher incidence of new compression fracture than do other vertebrae. Between March 2001 and December 2002, a total of 271 patients underwent vertebroplasty and a retrospective review of charts was performed. Patients reached 24 months of follow-up were included for analyses. Age, gender, bone mineral density, the numbers of prior vertebroplasty procedures, cement volume, postoperative kyphotic angle, the vertebral level, and kyphotic changes were assessed in relation to surgical outcome. The 220 patients had a mean age of 72.7 years (range, 53-97 years) and a mean follow-up interval of 25.6 months (range, 24-36 months). A total of 15 patients had 18 new fractures, and 11 new fractures were at the thoracolumbar junction (T12-L1) (p = 0.61). New fractures were in vertebrae adjacent to a treated vertebra in 55.6% (10 of 18 cases) of cases. Analysis of potential predictors for new vertebral fracture failed to identify statistically significant risk factors, despite a large sample size. Overall, 6.16% (18 of 292) of all treated vertebra developed associated new vertebral fractures. Cranial vertebrae were most likely to fracture at the adjacent level, whereas thoracic vertebrae were least likely to fracture at the adjacent level. Additional risk factors for new vertebral fracture are poorly understood.

Mild prevalent and incident vertebral fractures are risk factors for new fractures

This prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures. Mild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women. Three thousand three hundred and fifty-eight patients, aged 74 +/- 6 years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4 years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade >or= 2 fracture. These calculations were made for prevalent and then incident fractures. The RR of vertebral fracture in 4 years was 1.8 (1.3-2.4) p < 0.001, and 2.7 (2.3-3.3) p < 0.001 for patients having only mild vertebral fractures and at least one grade >or= 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1-2.6) p = 0.01, and 1.9 (1.3-2.6) p < 0.001 for patients having during the first 2 years incident mild fractures only, and for patients having at least one grade >or= 2 incident fracture respectively. The RR of non-vertebral fracture in 4 years was 1.3 (0.9-1.9) p = 0.15 and 1.7 (1.4-2.1) p < 0.001 for patients having only mild or at least one grade >or= 2 vertebral fracture at baseline respectively. For patients aged more than 70 years, these RR were 1.45 (0.99-2.11) (p = 0.06), and 1.72 (1.36-2.18) p < 0.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36-2.09) p < 0.001 for patients having at least one grade >or= 2 incident fracture during the 2 first years of follow-up. Mild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2 years will fracture again within the 2 next years.

Cement Leakage During Vertebroplasty Can Be Predicted on Preoperative MRI

Previous studies have shown that cement leakage into an adjacent disk space is a risk factor for new fracture after vertebroplasty. The purpose of this study was to investigate the use of preoperative MRI for predicting such cement leakage. Our institutional review board approved this retrospective study and waived the requirement of informed consent. We studied preoperative MRI of 46 vertebroplasty patients (107 vertebral bodies). Endplate cortical defect, abnormal T2 hyperintensity in adjacent disk space, intravertebral cleft, degree of compression, and wedge angle were correlated to the incidence of cement leakage into the adjacent disk. Patient age, sex, and location of treated vertebral body were also evaluated. We used logistic regression analysis and Fisher's exact probability test to analyze the association between cement leakage and these observations. Cortical defect in the endplate of the treated vertebral body, abnormal T2 hyperintensity in the adjacent intervertebral disk, and absence of intravertebral cleft were associated with cement leakage into the disk space (p < 0.05). There was no statistically significant association between cement leakage into the disk and degree of compression, wedge angle, location of treated vertebral body, patient age, or sex (p > 0.05). Cement leakage into an adjacent disk is more common when there is a cortical defect in the endplate and increased T2 signal in the adjacent disk and is less common if there is an intravertebral cleft.

Association of prevalent vertebral fractures, bone density, and alendronate treatment with incident vertebral fractures: effect of number and spinal location of fractures

Vertebral fractures are the most common osteoporotic fracture and are associated with significant pain and disability. Prior vertebral fracture and low bone mineral density (BMD) are strong predictors of new vertebral fracture. Using data from 6082 women, ages 55–80 years, in the Fracture Intervention Trial (a randomized, placebo-controlled trial of the antiresorptive agent, alendronate), we explored the association of the number of prior vertebral fractures with the risk of new fractures and whether this association is influenced by the spinal location of fractures. The risk of future vertebral fractures increased with the number of prevalent fractures, independently of age and BMD; in the placebo group, more than half of the women with five or more fractures at baseline developed new vertebral fractures, compared to only 3.8% of women without prior vertebral fractures. The magnitude of association with an increased risk of future vertebral fractures was equal for prevalent fractures located in either the “lower” (T12–L4) (relative risk [RR] = 2.9; 95% CI = 1.9, 3.6) or “upper” (T4–10) spine (RR = 2.6; 95% CI = 1.9, 3.6). We found no evidence that the effectiveness of alendronate in reducing the risk of future vertebral fracture was attenuated in women with up to five or more prevalent fractures, or that it varied by the location of prevalent fractures. However, prevalent vertebral fractures in any location were more strongly associated with risk of new fractures in the upper (RR = 5.2; 95% CI = 3.2, 8.3) than in the lower spine (2.3; 1.6, 3.3). In addition, each 1 SD decrease in spinal BMD was associated with a 2.1 (1.7, 2.6) times greater odds of new fracture in the upper spine, compared with 1.5 (1.3, 1.8) for the lower spine. These findings suggest that, in older women, osteoporosis may be a stronger risk factor for new fractures in the upper (vs. lower) thoracolumbar spine, although we found no evidence that the location of prior fractures should influence treatment decisions. Physicians should recognize that prior vertebral fractures are a strong risk factor for future fractures, and consider treating such patients to reduce their risk of subsequent fractures.

An earlier fracture as a risk factor for new fracture and its association with smoking and menopausal age in women

The purpose of this study was to investigate whether a previous fracture is a risk factor for fracture later in life and its association with tobacco smoking, menopausal age and the use of oral contraceptives. This is an epidemiological population study based on a questionnaire. A sample of 10000 women from seven birth cohorts between 1900-1940 was obtained at random from the population register. The overall response rate was 74.6%. The responders (n = 7459) represented 53% of the total population. The women from all these birth cohorts were questioned regarding a possible history of fractures and the year in which they were sustained. The questionnaire also included questions about menopausal age, use of oral contraceptives, previous gynaecological operations and possible oestrogen medication. The women from the 1900-1920 birth cohorts were questioned in detail about urogenital disorders, while tobacco smoking data were recorded only for the 1930 and 1940 birth cohorts. The relative risk of sustaining a further fracture was significantly related to fracture premenopausally before 40 years of age and later fracture postmenopausally after 60 years of age (1.29; 0.97-1.70) compared to controls (0.78; 0.59-1.03)(P = 0.03). Both an early menopause and tobacco smoking were associated significantly with repeated fractures, while use of oral contraceptives had a protective effect against repeated fractures in the 1940 birth cohort. Logistic multiple regression showed that a fracture was a significant independent risk factor for further fracture in both cohorts 1900-1920 (P < 0.01) and 1930-1940 (P < 0.05). This study suggests poorer protective resources against new fractures among women with previous fractures, and that lack of oestrogen menopausally can partly explain the enhanced risk of fracture, not only during the menopause but also later in life when a hip fracture may have immense consequences. The results should draw our attention to emphasise the need for active treatment of patients with established osteoporosis because of the increased risk of new fractures later in life.