Incidence Of New Nonvertebral Fractures Research Articles

Treatment of high fracture risk patients in routine clinical practice

This paper describes the various medical therapy regimens prescribed to osteoporotic patients with high fracture risk and the result of treatment. We carried out a retrospective cohort study in selected Osteoporosis Centers. Patients were considered to have high fracture risk in case of a history of a low-energy hip fracture or two or more vertebral or other site fractures. A total of 812 subjects (768 women and 44 men) aged 36-95years were included. The observation period was 2285.1 patient-years. Demographic data, clinical findings, and BMD data obtained by DXA, as well as a history of fractures that had occurred during the follow-up, were included in the analysis. Overall, at baseline, there were 637 non-vertebral fractures including 104 hip fractures. A total of 590 patients had vertebral fractures; of these, 69% suffered multiple fractures. Being on treatment, 119 (14.7%) patients developed new vertebral and non-vertebral fractures. The incidence of new non-vertebral fractures and hip fractures was 39.4 and 13.1 per 1000 patient-years. The total number of vertebral fractures increased by 24.8% from 1353 to 1689. The best results of the treatment were achieved in patients who were started on zoledronic acid, denosumab, or teriparatide and had an adequate duration of treatment. Although these patients had significantly lower BMD values at the time of diagnosis compared with other patients, they showed a lower incidence of new vertebral and hip fractures, during the follow-up. Therapy of patients at high risk of fractures started with more potent treatment regimens (zoledronic acid, denosumab and/or teriparatide) of adequate duration was more effective in terms of prevention of new vertebral and hip fractures as compared with other treatment options. However, treatment appears to be challenging given the number of recurrent fractures in patients on treatment and the frequency of drug withdrawal or replacement.

Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men.

Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men.

Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients

Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group (n=158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311-315, 2009). In that study, we treated daily those controls with prevalent vertebral fractures with 1μg alfacalcidol+500mg calcium (group A) and those without prevalent vertebral fractures with 1,000IU plain vitamin D (Vit. D)+1,000mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8%) and total hip BMD (+1.9 vs. -0.9%) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D (p=0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60ml/min (p=0.0019). There were no serious adverse events (SAE), and the numbers of mild-to-moderate adverse events (AE) were not different between groups. Despite the higher initial fracture risk in the alfacalcidol group, 2-year treatment with this active D-hormone prodrug showed a higher therapeutic efficacy in terms of BMD, falls and fractures. One important advantage of alfacalcidol may be that it is effective even in patients with mild-to-moderate renal insufficiency.

HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial

Objectives We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D 3 supplementation in a 5-year prospective trial. Methods A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth year); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. Results Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle ( P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042) than women receiving placebo and also after adjusting as above ( P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased ( P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10–0.90) and with Vit D 0.47 (95% CI, 0.20–1.14) and with HRT + Vit D 0.44 (95% CI, 0.17–1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). Conclusions This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.

Effects of Bisphosphonates on Fracture Incidence and Bone Metabolism in Rheumatoid Arthritis Patients in General Practice Taking Long-Term Corticosteroid Therapy

There is a risk that disturbances of activities of daily living (ADL) due to rheumatoid arthritis (RA) are increased by the occurrence of fractures, including vertebral compression fractures and femoral neck fractures, in RA patients receiving oral corticosteroid therapy. Bisphosphonates are most commonly used in the treatment of postmenopausal osteoporosis. In a large-scale, randomized, double-blind, placebo-controlled study that was performed to assess the prophylactic efficacy of bisphosphonates, alendronic acid decreased the incidence of vertebral fractures by approximately 50% compared with placebo in postmenopausal patients. A similar result has also been reported with risedronic acid. The present long-term retrospective study evaluated the effects of alendronic acid and risedronic acid therapy on development of new vertebral/non-vertebral fractures in RA patients receiving long-term oral prednisolone therapy at an average dose of 5 mg/day. The subjects were 138 general practice patients aged 50-79 years with RA (alendronic acid group 80; risedronic acid group 58) who received oral prednisolone at a dose of 2-15 mg/day for at least 1 year combined with bisphosphonate therapy (alendronic acid 5 mg/day or risedronic acid 2.5 mg/day) for at least 10 months. Patients with five or more vertebral fractures at the start of bisphosphonate therapy were excluded from the study. Vertebral fractures were detected by obtaining plain x-ray films of the thoracic and lumbar spines at the start of bisphosphonate therapy and on completion of follow-up. We measured the incidence of new fractures, the speed of sound (SOS) at the calcaneus as measured by quantitative ultrasound, and levels of crosslinked N-telopeptide of type I collagen (NTX), a marker of bone resorption. The percentage change at each measuring point was tested using the paired t-test. The incidence of new fractures was compared between groups using the Cox proportional hazard model. The incidence of new vertebral fractures was 6.3% in the alendronic acid group and 13.8% in the risedronic acid group; the incidence of new non-vertebral fractures was 6.3% and 12.1%, respectively. The incidence of any fracture was significantly higher and severe fractures tended to be more common in the risedronic acid group. Analysis by the Cox proportional hazard model revealed a significant difference between the two groups with respect to the cumulative incidence of new fractures (p = 0.0386). The SOS of the calcaneus showed no appreciable difference between the two groups. NTX measurements indicated that antiresorptive activity was maintained from 6 months of treatment onwards in the alendronic acid group but not in the risedronic acid group. These findings suggest that alendronic acid has a stronger prophylactic effect against fractures than risedronic acid in RA general practice patients taking long-term corticosteroid therapy.

Relationship between Bone Mineral Density Changes and Fracture Risk Reduction in Patients Treated with Strontium Ranelate

Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate. Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated. The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation. After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04). During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.

HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial

Objectives: We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D 3 supplementation in a 5-year prospective trial. Methods: A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n=13100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth year); (3) HRT+Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. Results: Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT+Vit D 8 and placebo 17). The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P=0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle ( P=0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures ( P=0.042) than women receiving placebo and also after adjusting as above ( P=0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased ( P=0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10–0.90) and with Vit D 0.47 (95% CI, 0.20–1.14) and with HRT+Vit D 0.44 (95% CI, 0.17–1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). Conclusions: This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.