Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture.

BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic-acid group (P = 0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS: An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival. (ClinicalTrials.gov number, NCT00046254.).

Analysis of joint laxity after total ankle arthroplasty: cadaver study.

BACKGROUND: Clinical results of total ankle arthroplasty with early designs were disappointing. Recently-developed ankle prostheses have good mid-term results; however, limited information is available regarding effects of total ankle arthroplasty on ankle laxity. METHODS: Eight cadaveric lower extremities were tested with a custom device which enabled measurement of multi-axial forces, moments, and displacement during applied axial, shear, and rotational loading. Tests consisted of anterior-posterior and medial-lateral translation and internal-external rotation of the talus relative to the tibia during axial loads on the tibia simulating body weight (700 N) and an unloaded condition (5 N). Tests were performed in neutral, dorsiflexion, and plantarflexion. Laxity was determined for the intact ankle, and following insertion of an unconstrained total ankle implant, comparing load-displacement curve. FINDINGS: Laxity after total ankle arthroplasty did not approximate the normal ankle in most conditions tested. Displacement was significantly greater for total ankle arthroplasty in both posterior and lateral translation, and internal rotation, with 5 N axial loading, and anterior-posterior, medial-lateral translation, and internal-external rotation for 700 N axial loading. For the 700 N axial load condition, in the neutral ankle position, total anterior-posterior translation averaged 0.4 mm (SD 0.2 mm), but 6.0 mm (SD 1.5 mm) after total ankle arthroplasty (P<0.01). This study demonstrated more laxity in the replaced ankle than normal ankle for both unloaded and 700 N axially loaded conditions. INTERPRETATION: These data indicate the increased responsibility of the ligaments for ankle laxity after total ankle arthroplasty and suggest the importance of meticulous ligament reconstruction with total ankle arthroplasty operations.

Immediate hip spica is as effective as, but more efficient than, flexible intramedullary nailing for femoral shaft fractures in pre-school children.

Flexible intramedullary nailing (FIN) is the gold standard treatment for femur fracture in school-aged children. It has been performed successfully in younger children, although Spica cast immobilisation (SCI) has been the most widely used strategy to date. METHOD: A retrospective analysis was performed between two comparable groups of children aged 1-4 years with a femoral shaft fracture. Two University hospitals, each using specific treatment guidelines, participated in the study: SCI in Group I (Basel, Switzerland) and FIN in Group II (Lausanne, Switzerland). RESULTS: Group I included 19 children with a median age of 26 months (range 12-46 months). Median hospital stay was 1 day (range 0-5 days) and casts were retained for a median duration of 21 days (range 12-29 days). General anaesthesia was used in six children and sedation in four. Skin breakdown secondary to cast irritation occurred in two children (10.5%). The median follow-up was 114 months (range 37-171 months). No significant malunion was noted. Group II included 27 children with a median age of 38.4 months (range 18.7-46.7 months). Median hospital stay was 4 days (range 1-13 days). All children required general anaesthesia for insertion and removal of the nails. Free mobilisation and full weight bearing were allowed at a median of 2 days (range 1-10 days) and 7 days (range 1-30 days), respectively, postoperatively. Nail exteriorisation was noted in three children (11%). The median follow-up was 16.5 months (range 8-172 months). No significant malunion was reported. CONCLUSIONS: Young children with a femoral shaft fracture treated by SCI or FIN had similarly favourable outcomes and complication rates. FIN allowed earlier mobilisation and full weight bearing. Compared to SCI, a greater number of children required general anaesthesia. In a pre-school child with a femoral shaft fracture, immediate SCI applied by a paediatric orthopaedic team following specific guidelines allowed early discharge from hospital with few complications.

Prothèses totales de genoux. Analyse clinique et numérique des micromouvements de l'implant tibial [Total knee prosthesis. Clinical and numerical study of micromovements of the tibial implant].

INTRODUCTION: The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant. MATERIAL AND METHODS: Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms. The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the micromovements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion. RESULTS: 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present. Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns). DISCUSSION: Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established. Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

FRAX(®) Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry International Osteoporosis Foundation Position Development Conference.

FRAX(®) is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX(®) is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX(®) into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX(®) in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX(®) input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX(®) Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX(®)-related issues.

R6le de l'urotlogue dans le dépistage des maladies osseuses [Role of the urologist in the screening of bone diseases].

During their lifetime, 20% of men will suffer from a fracture secondary to osteoporosis, and morbidity and mortality of a hip fracture in men are more severe than in women. Despite these facts, there are only few studies on osteoporosis in men. Hyopgonadism is a known risk factor for bone mineral density decrease. Hypogonadism can be found in patients diagnosed with prostate cancer who are receiving androgen deprivation therapy, but can also be discovered in patients with male infertility or erectile dysfunction. Urologists have central role in men's health aftercare, and therefore have key role in the screening and in the multidisciplinary treatment of osteoporosis and osteopenia.

3-year follow-up results of bone mineral content and density after a school-based physical activity randomized intervention trial.

BACKGROUND: As an important modifiable lifestyle factor in osteoporosis prevention, physical activity has been shown to positively influence bone mass accrual during growth. We have previously shown that a nine month general school based physical activity intervention increased bone mineral content (BMC) and density (aBMD) in primary school children. From a public health perspective, a major key issue is whether these effects persist during adolescence. We therefore measured BMC and aBMD three years after cessation of the intervention to investigate whether the beneficial short-term effects persisted. METHODS: All children from 28 randomly selected first and fifth grade classes (intervention group (INT): 16 classes, n=297; control group (CON): 12 classes, n=205) who had participated in KISS (Kinder-und Jugendsportstudie) were contacted three years after cessation of the intervention program. The intervention included daily physical education with daily impact loading activities over nine months. Measurements included anthropometry, vigorous physical activity (VPA) by accelerometers, and BMC/aBMD for total body, femoral neck, total hip, and lumbar spine by dual-energy X-ray absorptiometry (DXA). Sex- and age-adjusted Z-scores of BMC or aBMD at follow-up were regressed on intervention (1 vs. 0), the respective Z-score at baseline, gender, follow-up height and weight, pubertal stage at follow-up, previous and current VPA, adjusting for clustering within schools. RESULTS: 377 of 502 (75%) children participated in baseline DXA measurements and of those, 214 (57%) participated to follow-up. At follow-up INT showed significantly higher Z-scores of BMC at total body (adjusted group difference: 0.157 units (0.031-0.283); p=0.015), femoral neck (0.205 (0.007-0.402); p=0.042) and at total hip (0.195 (0.036 to 0.353); p=0.016) and higher Z-scores of aBMD for total body (0.167 (0.016 to 0.317); p=0.030) compared to CON, representing 6-8% higher values for children in the INT. No differences could be found for the remaining bone parameters. For the subpopulation with baseline VPA (n=163), effect sizes became stronger after baseline VPA adjustment. After adjustment for baseline and current VPA (n=101), intervention effects were no longer significant, while effect sizes remained the same as without adjustment for VPA. CONCLUSION: Beneficial effects on BMC of a nine month general physical activity intervention appeared to persist over three years. Part of the maintained effects may be explained by current physical activity.

Smart instrumentation for determination of ligament stiffness and ligament balance in total knee arthroplasty.

Ligament balance is an important and subjective task performed during total knee arthroplasty (TKA) procedure. For this reason, it is desirable to develop instruments to quantitatively assess the soft-tissue balance since excessive imbalance can accelerate prosthesis wear and lead to early surgical revision. The instrumented distractor proposed in this study can assist surgeons on performing ligament balance by measuring the distraction gap and applied load. Also the device allows the determination of the ligament stiffness which can contribute a better understanding of the intrinsic mechanical behavior of the knee joint. Instrumentation of the device involved the use of hall-sensors for measuring the distractor displacement and strain gauges to transduce the force. The sensors were calibrated and tested to demonstrate their suitability for surgical use. Results show the distraction gap can be measured reliably with 0.1mm accuracy and the distractive loads could be assessed with an accuracy in the range of 4N. These characteristics are consistent with those have been proposed, in this work, for a device that could assist on performing ligament balance while permitting surgeons evaluation based on his experience. Preliminary results from in vitro tests were in accordance with expected stiffness values for medial collateral ligament (MCL) and lateral collateral ligament (LCL).

Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study.

Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.

Combining clinical factors and quantitative ultrasound improves the detection of women both at low and high risk for hip fracture.

We hypothesized that combining clinical risk factors (CRF) with the heel stiffness index (SI) measured via quantitative ultrasound (QUS) would improve the detection of women both at low and high risk for hip fracture. Categorizing women by risk score improved the specificity of detection to 42.4%, versus 33.8% using CRF alone and 38.4% using the SI alone. This combined CRF-SI score could be used wherever and whenever DXA is not readily accessible. INTRODUCTION AND HYPOTHESIS: Several strategies have been proposed to identify women at high risk for osteoporosis-related fractures; we wanted to investigate whether combining clinical risk factors (CRF) and heel QUS parameters could provide a more accurate tool to identify women at both low and high risk for hip fracture than either CRF or QUS alone. METHODS: We pooled two Caucasian cohorts, EPIDOS and SEMOF, into a large database named "EPISEM", in which 12,064 women, 70 to 100 years old, were analyzed. Amongst all the CRF available in EPISEM, we used only the ones which were statistically significant in a Cox multivariate model. Then, we constructed a risk score, by combining the QUS-derived heel stiffness index (SI) and the following seven CRF: patient age, body mass index (BMI), fracture history, fall history, diabetes history, chair-test results, and past estrogen treatment. RESULTS: Using the composite SI-CRF score, 42% of the women who did not report a hip fracture were found to be at low risk at baseline, and 57% of those who subsequently sustained a fracture were at high risk. Using the SI alone, corresponding percentages were 38% and 52%; using CRF alone, 34% and 53%. The number of subjects in the intermediate group was reduced from 5,400 (including 112 hip fractures) and 5,032 (including 111 hip fractures) to 4,549 (including 100 including fractures) for the CRF and QUS alone versus the combination score. CONCLUSIONS: Combining clinical risk factors to heel bone ultrasound appears to correctly identify more women at low risk for hip fracture than either the stiffness index or the CRF alone; it improves the detection of women both at low and high risk.

Modelling Bone Mineral Density in Swiss Breast Cancer Patients Treated with Letrozole, Tamoxifen and Sequences of Letrozole and Tamoxifen in the BIG 1-98 Study (SAKK 21/07).

Background: Bone health is a concern when treating early stage breast cancer patients with adjuvant aromatase inhibitors. Early detection of patients (pts) at risk of osteoporosis and fractures may be helpful for starting preventive therapies and selecting the most appropriate endocrine therapy schedule. We present statistical models describing the evolution of lumbar and hip bone mineral density (BMD) in pts treated with tamoxifen (T), letrozole (L) and sequences of T and L. Methods: Available dual-energy x-ray absorptiometry exams (DXA) of pts treated in trial BIG 1-98 were retrospectively collected from Swiss centers. Treatment arms: A) T for 5 years, B) L for 5 years, C) 2 years of T followed by 3 years of L and, D) 2 years of L followed by 3 years of T. Pts without DXA were used as a control for detecting selection biases. Patients randomized to arm A were subsequently allowed an unplanned switch from T to L. Allowing for variations between DXA machines and centres, two repeated measures models, using a covariance structure that allow for different times between DXA, were used to estimate changes in hip and lumbar BMD (g/cm2) from trial randomization. Prospectively defined covariates, considered as fixed effects in the multivariable models in an intention to treat analysis, at the time of trial randomization were: age, height, weight, hysterectomy, race, known osteoporosis, tobacco use, prior bone fracture, prior hormone replacement therapy (HRT), bisphosphonate use and previous neo-/adjuvant chemotherapy (ChT). Similarly, the T-scores for lumbar and hip BMD measurements were modeled using a per-protocol approach (allowing for treatment switch in arm A), specifically studying the effect of each therapy upon T-score percentage. Results: A total of 247 out of 546 pts had between 1 and 5 DXA; a total of 576 DXA were collected. Number of DXA measurements per arm were; arm A 133, B 137, C 141 and D 135. The median follow-up time was 5.8 years. Significant factors positively correlated with lumbar and hip BMD in the multivariate analysis were weight, previous HRT use, neo-/adjuvant ChT, hysterectomy and height. Significant negatively correlated factors in the models were osteoporosis, treatment arm (B/C/D vs. A), time since endocrine therapy start, age and smoking (current vs. never).Modeling the T-score percentage, differences from T to L were -4.199% (p = 0.036) and -4.907% (p = 0.025) for the hip and lumbar measurements respectively, before any treatment switch occurred. Conclusions: Our statistical models describe the lumbar and hip BMD evolution for pts treated with L and/or T. The results of both localisations confirm that, contrary to expectation, the sequential schedules do not seem less detrimental for the BMD than L monotherapy. The estimated difference in BMD T-score percent is at least 4% from T to L.

Sub- or intertrochanteric fracture following screw fixation of an intracapsular proximal femoral fracture: true complication or technical error?

PURPOSE: To review, retrospectively, the possible causes of sub- or intertrochanteric fractures after screw fixation of intracapsular fractures of the proximal femur. METHODS: Eighty-four patients with an intracapsular fracture of proximal femur were operated between 1995 and 1998 by using three cannulated 6.25 mm screws. The screws were inserted in a triangular configuration, one screw in the upper part of the femoral neck and two screws in the inferior part. Between 1999 and 2001, we use two screws proximally and one screw distally. RESULTS: In the first series, two patients died within one week after operation. Sixty-four fractures healed without problems. Four patients developed an atrophic non-union; avascular necrosis of the femoral head was found in 11 patients. Three patients (3.6%) suffered a sub- and/or intertrochanteric fracture after a mean postoperative time of 30 days, in one case without obvious trauma. In all three cases surgical revision was necessary. Between 1999 and 2001 we did not observe any fracture after screwing. CONCLUSION: Two screws in the inferior part of the femoral neck create a stress riser in the subtrochanteric region, potentially inducing a fracture in the weakened bone. For internal fixation for proximal intracapsular femoral fracture only one screw must be inserted in the inferior part of neck.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.

CONTEXT: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk. OBJECTIVE: The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment. DESIGN, SETTING, AND PATIENTS: We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis. Intervention: A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months. MAIN OUTCOME MEASURES: Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications. RESULTS: Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index >or= 25 kg/m(2) (P = 0.02). There were no significant treatment-factor interactions for hip or nonvertebral fracture or for change in BMD. CONCLUSIONS: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.