Osteoporosis Vertebral Fractures Research Articles

Vertebroplasty in the treatment of osteoporosis vertebral fractures: Report on 52 cases

Percutaneous vertebroplasty (PV) is largely employed in vertebral body compression fractures (VCF). To evaluate the efficacy of PV on pain relief and functional status, and its complications rate. A prospective observational study was conducted by the Division of Internal Medicine of St. Croce and Carle Hospital. Diagnosis of osteoporosis, intense back pain, unresponsive to conservative treatment, associated with radiological evidence of recent VCF. Pain control and functional improvement were respectively assessed using Visual Analogue Scale (VAS) and Activity of Daily Living scale (ADL) on admission, 24 h after PV and at follow-up. PV complications were detected by an immediate computed tomography (CT) scan on the vertebra treated as well as the vertebrae above and below the treated level(s) and by CT chest scan to exclude pulmonary emboli. A magnetic resonance imaging (MRI) follow-up at 6 or 12 months was performed. Fifty-two (46 with primary osteoporosis) patients were enrolled (mean age 73.18 yr, range 44-92). Median follow-up was 20.4 months (range 6-24). Treated vertebrae were 124. VAS, mean value was 9.05 (range 6-10) before treatment, 5.95 (range 2-8) at 24 h after PV and 4.94 (range 2-9) at follow-up (p<0.001). Before PV, 18 patients (34.6%) were functionally impaired vs 8 patients (15.3%) at follow-up (p<0.003). Control MRI evidenced 9 (17.3%) new VCF adjacent and 13 (25%) non-adjacent to treated vertebras. There was one case of discitis. Seven cases (13%) of cement leakage in para-vertebral space were observed. PV is safe and effective in immediate pain reduction and functional improvement and at a median term follow-up.

Back pain in osteoporotic vertebral fractures

This review article examines the epidemiology and pathogenesis of back pain and vertebral fractures in osteoporosis, reviewing the management of pain in patients with vertebral fractures and the direct and indirect effect of osteoporosis treatments on back pain. The management of patients with vertebral fractures has largely concentrated on the prevention of further fractures by the treatment of underlying osteoporosis, with drug treatment for acute and chronic back pain and the non-pharmacological management of vertebral fractures receiving less attention. Emerging evidence suggests that, in addition to reducing the incidence of vertebral fractures, calcitonin, intravenous bisphosphonates and teriparatide may also have a direct effect on bone pain. Targeted analgesia, tailored to individual need is often required in both the acute and chronic phases following vertebral fracture. Vertebroplasty and kyphoplasty have also been approved for use in the management of vertebral fractures and may prove useful in selected patients unresponsive to conventional pain relief. There is some evidence to support the use of individualised tailored exercise programmes aimed at strengthening back muscles to maintain bone density and reduce further fracture incidence. In addition the use of specific orthoses may help to reduce kyphosis, improve mobility and reduce pain. Chronic back pain associated with vertebral fracture provides a great challenge to health care professionals and the patient. This demands a combination of options, including not only therapeutic interventions, but also physiotherapy, psychological support and patient education.

Recombinant PTH May Prevent Vertebral Fractures in Osteoporosis

In a previous study, recombinant human parathyroid hormone (PTH; teriparatide, or Forteo) increased bone-mineral density (BMD) and reduced the incidence of new vertebral fractures among postmenopausal women with prior vertebral fractures (Journal Watch May 18 2001). In this new multinational trial, researchers examined the effect of PTH on the incidence of fracture in 2679 …

Outcomes of a nurse-led osteoporosis and falls assessment

Osteoporosis is a major public health concern. Recent evidence from clinical and epidemiological trials on osteoporosis has stressed the urgency for early and accurate diagnosis of vertebral fractures. Despite the fact that vertebral fractures are very common and associated with decreased quality of life, they are frequently missed in daily clinical practice. The authors developed a protocol to be applied through a specialized nurse-led osteoporosis vertebral fracture service that allows for accurate diagnosis, identifies patients at risk and shortens the time of assessment and management. A total of 114 patients have been reviewed over 12 months. Completing the referral form and the clinic proforma helped the nurse cover all causes of vertebral fractures and shortened the lag time for assessment and management. Osteoporosis therapy was commenced once diagnosis was confirmed.

Ibandronate: Once-Monthly and Intravenous Dosing Options for Osteoporosis Treatment

Ibandronate is a potent nitrogen-containing bisphosphonate that is currently available as a daily and once-monthly oral formulation for the treatment and prevention of osteoporosis. It has recently been approved for intermittent intravenous administration. The oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe (BONE), Monthly Oral iBandronate In LadiEs (MOBILE), and Dosing IntraVenous Administration (DIVA) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density and reducing markers of bone turnover. BONE demonstrated that ibandronate reduced the risk of new vertebral fractures and reduced the relative risk of nonvertebral fractures in higher-risk patients. Histomorphometric evaluations in the BONE and DIVA trials have demonstrated that bone quality is maintained following treatment. Giving patients the option of choosing their dose regimen and route of administration may increase overall adherence to treatment, leading to enhanced fracture protection in patients with osteoporosis.

Beyond daily dosing: Clinical experience

Osteoporosis has had a significant public health impact, with many sufferers experiencing fractures. Such fractures lead to increased disability, mortality and reduced quality of life, all of which raise healthcare costs. Oral bisphosphonates are associated with significant antifracture efficacy and have therefore become the mainstay of treatment for postmenopausal osteoporosis. Poor therapeutic adherence with daily bisphosphonates has been improved by the introduction of weekly regimens, although adherence levels remain suboptimal. Bisphosphonate regimens with dosing intervals beyond a week have therefore been developed to address this issue. Oral ibandronate, a potent nitrogen-containing bisphosphonate, has been studied using daily and intermittent regimens (between-dose interval >2 months). The initial phase II 2-year study confirmed the feasibility of the intermittent regimen, providing increases in lumbar spine bone mineral density (BMD) superior to placebo ( P < 0.01) and equivalent to the daily regimen (5.64% vs. 5.54%, respectively). BONE (Oral i Bandronate Osteoporosis vertebral fracture trial in North America and Europe), a large phase III 3-year study was subsequently initiated, including 2946 women with postmenopausal osteoporosis and testing both a daily as well as an intermittent regimen with a dose-free interval of more than 2 months. Significant vertebral antifracture efficacy (the primary study endpoint) was demonstrated with daily (2.5 mg) and intermittent (20 mg every other day for 12 doses every 3 months) ibandronate in comparison with placebo ( P ≤ 0.0006). As a result of the study not being designed and powered to show an effect on non-vertebral fractures and the overall population being at low risk for osteoporotic fractures, differences in the incidence of non-vertebral fractures were similar between groups (8.2-9.1%) However, a post hoc analysis in a subgroup of patients with a femoral neck BMD T-score < −3.0 showed that daily ibandronate significantly reduced the risk of non-vertebral fractures ( P = 0.012). Both regimens were associated with significant increases in lumbar spine and proximal femur BMD and normalization of bone turnover. As determined by adverse event incidence and laboratory evaluation, the safety profile for both ibandronate regimens was similar to that observed for placebo. The BONE study therefore confirmed that daily or intermittent ibandronate is an effective and well-tolerated treatment for postmenopausal women. Being the first study to demonstrate antifracture efficacy with an intermittent regimen, it provided ‘proof of concept’ for beyond weekly dosing with ibandronate and prompted further development of a more convenient once-monthly regimen.

Ibandronate treatment for osteoporosis: Rationale, preclinical and clinical development of extended dosing regimens

Ibandronate is a potent nitrogen-containing bisphosphonate available as a once-monthly oral formulation for the treatment and prevention of osteoporosis. Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing. Initial clinical trials explored the optimal dosing regimens for oral administration in humans. The Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) and Monthly Oral Ibandronate in Ladies (MOBILE) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density, reducing markers of bone turnover, and preventing fractures, while maintaining bone quality. These preclinical and clinical ibandronate trials provided progressive evidence that a simple, long interval dosing regimen could offer efficacy and safety comparable with currently available bisphosphonates. It is anticipated that once-monthly ibandronate may have a positive impact on patient adherence, and ultimately, on fracture protection in osteoporotic women.

Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and 3 years in postmenopausal women with osteoporosis

In a recent multinational, double-blind, placebo-controlled, randomized, phase III study (BONE: IBandronate Osteoporosis Vertebral Fracture trial in North America and Europe), oral daily ibandronate (2.5 mg) significantly and substantially reduced the risk of new vertebral fractures by 62% relative to placebo after 3 years of treatment. The objective of the present study was to retrospectively analyze data from the BONE study to examine the efficacy of oral ibandronate in preventing incident vertebral fractures of greater severity. This analysis was conducted on the placebo and oral daily ibandronate (2.5 mg) arms of the BONE study, comprising a total of 1964 women (aged 55–80 years, ≥5 years postmenopause) with osteoporosis. Vertebral fractures on annual lateral radiographs of the spine were graded as mild, moderate, or severe, using criteria derived from an established semiquantitative technique. The findings demonstrate that in addition to being effective in significantly reducing the risk of new vertebral fractures of all severities, oral daily ibandronate has a pronounced effect on the more severe, most clinically relevant, vertebral fractures: a significant and sustained reduction of 59% in the relative risk of combined new moderate and severe vertebral fractures was observed at years 1 ( P = 0.0164), 2 ( P = 0.0004), and 3 ( P < 0.0001).

Ibandronate produces significant, similar antifracture efficacy in North American and European women: new clinical findings from BONE

ABSTRACTObjectives: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2 months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here.Patients and methods: BONE was a randomized, double-blind, placebo-controlled, fracture-prevention study in 2946 postmenopausal women (age 55 years−80 years; ≥ 5 years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4−L4]). Participants received daily calcium (500 mg) and vitamin D (400 IU) plus either placebo, oral daily ibandronate (2.5 mg) or oral intermittent ibandronate (20 mg every other day for 12 doses every 3 months). The efficacy and tolerability of ibandronate were assessed independently in both North American and European populations.Results: Consistent, significant efficacy was observed in the North American (new vertebral fracture risk reduction: 60% and 54% with daily and intermittent ibandronate, respectively) and European patient populations (50% and 48%, respectively). Both ibandronate regimens also significantly reduced the incidence of new, worsening, and acute clinical, vertebral fractures. Daily and intermittent ibandronate significantly increased bone density at the spine in both North American (5.4% and 4.4% vs. baseline with daily and intermittent ibandronate, respectively) and European (7.1% and 6.3% vs. baseline, respectively) populations. Significant increases were also observed for total hip bone density (2.6% and 3.7% vs. baseline for daily, and 2.5% and 3.1% for intermittent; North American and European populations, respectively). Comparable, significant decreases in biochemical markers of bone turnover (reductions in urinary excretion of C-telopeptide levels of 53.5% and 67.1% vs. baseline for daily, and 50.0% and 53.8% for intermittent; North American and European populations, respectively) were also observed in both populations ( p < 0.004 for all cited measurements in each ibandronate group vs. placebo). Oral ibandronate was well tolerated in both North American and European patients, with a safety profile similar to placebo.Conclusions: Oral ibandronate, administered daily or intermittently, effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis. These results demonstrate the efficacy of ibandronate administered with extended dose-free intervals, regardless of patients’ geographical origin. Research investigating other less frequent ibandronate regimens, such as once-monthly oral administration, is underway.

Acute Pericarditis Caused by Acrylic Bone Cement After Percutaneous Vertebroplasty

Acute pericarditis caused by foreign material without trauma is rare. In the following case, acrylic bone cement penetrated the right ventricle (RV) after percutaneous vertebroplasty (PVP). A 66-year-old woman presented with chest pain exacerbated by deep inspiration and recumbency. She had received PVP 8 days earlier to treat a vertebral compression fracture. Her chest radiograph showed fractured vertebra filled with bone cement in …

Vitamin D receptor genotypes influence the success of calcitriol therapy for recurrent vertebral fracture in osteoporosis

Osteoporosis is a complex multi-factorial disease where environment, diet and genetics play a role in determining susceptibility. Patients with existing vertebral fracture have a heightened risk of further recurrent vertebral fracture. The efficacy of new osteoporosis therapies is often compared to calcium supplementation. 1,25-dihydroxyvitamin D3 (calcitriol) acts through the vitamin D receptor (VDR) and is effective at reducing recurrent vertebral fracture risk. Because the VDR controls calcium metabolism, we hypothesized that genetic variation at the VDR locus may influence response to both calcium and calcitriol therapy. Postmenopausal women with osteoporosis from a 3-year study comparing calcitriol versus calcium for prevention of vertebral fractures were genotyped for VDR alleles detected by FokI, BsmI, ApaI and TaqI. Data were analysed by hierarchical log-linear analysis and robust analysis of variance for relationships to fracture outcomes. Significant differences in the vertebral fracture rate in response to calcium therapy were observed between VDR genotypes (P<0.001). Calcium appeared to be equally effective as calcitriol in particular genotypes. The response to calcitriol therapy was most pronounced in patients carrying the TaqI t allele in combination with the FokI f initiation codon variant: f+t+ carriers were 11.3-fold less likely to sustain recurrent vertebral fracture in the last 2 years of the trial while on calcitriol therapy compared to calcium (P=1.4x10(-5)). Response to both calcium and calcitriol therapy is dependent on genetic variation at the VDR locus and two loci in the VDR gene may contribute to this effect.

Calcitonin for osteoporosis and bone pain.

Calcitonin has been approved for the treatment of osteoporosis and other diseases involving accelerated bone turnover for approximately 25 years. The most commonly studied and prescribed form is salmon calcitonin, which has a greater efficacy in clinical use. A wealth of well-controlled clinical studies have demonstrated that calcitonin preserves or increases bone mineral density (BMD) and reduces the risk of vertebral fractures in osteoporosis. Recent studies have indicated that while a low BMD is correlated with an increase in fracture risk, increases in BMD alone do not explain the antifracture efficacy of antiresorptive therapies such as calcitonin. Therapies that moderately increase BMD may reduce fracture risk by reducing the rate of bone turnover and maintaining the integrity of the trabecular architecture, resulting in the preservation of bone strength and quality in osteoporotic patients. An advantage of calcitonin that is not shared by other antiresorptive therapies is its direct analgesic effect on bone pain. Calcitonin has been demonstrated to be clinically useful in improving pain, not only from the acute vertebral fractures of osteoporosis, but also in Paget's disease, bone malignancies, and other sources of musculoskeletal pain. Drugs containing calcitonin may be approved for additional indications in the near future, and as more convenient routes of administration such as the oral route become available, the demand for the calcitonin peptide is expected to increase.

Identification of vertebral fractures in osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and microarchitectural deterioration. These lead to subsequent increase in bone fragility and susceptibility to low-trauma or atraumatic fractures, most commonly vertebral fractures but also fractures of hip and wrist. These have a significant impact on morbidity, mortality, and health care cost. Studies have demonstrated that the presence of vertebral fractures is an independent and significant predictor of the increased risk for further fractures. The occurrence of a vertebral fracture is often clinically asymptomatic, and many of these fractures, therefore, remain undiagnosed. Recently, a number of techniques have been developed that allow for reliable identification of vertebral fractures on radiographs. The two most widely used methods in clinical research are the semiquantitative assessment of vertebral deformities, which is based on visual evaluation, and the quantitative approach, which is based on different morphometric criteria. In our practice for osteoporosis evaluation we use the Genant semiquantitative approach-an accurate and reproducible method, tested and applied in many clinical studies. The newest generation of fan-beam dual energy X-ray absorptiometry (DXA) systems delivering "high-resolution" lateral spine images offer a potential practical alternative to radiographs for clinical vertebral fracture analysis. The advantages of using DXA over conventional X-ray devices are its minimal radiation exposure and high-speed image acquisition. It also allows combined evaluation of vertebral fracture status and bone mineral density, which could become a standard for patient assessment in osteoporosis.

Bone substitutes in vertebroplasty.

Vertebroplasty--percutaneous cement augmentation of vertebral bodies--is an efficient procedure for the treatment of painful vertebral fractures in osteoporosis. At the present time, polymethylmethacrylate (PMMA) is the only available cement with reports of clinical application and experience. The material is easy to handle, the radiopacity can be adapted by adding contrast dye, and it is mechanically efficient. Composite cements (acrylic cements in conjunction with ceramics) are bioactive, highly radiopaque, and feature excellent mechanical properties. One such cement, Cortoss, is currently undergoing clinical trials for vertebroplasty and has so far been shown to be a potentially valuable alternative to PMMA. Several in vitro studies with injectable calcium phosphate (CaP) cements show their feasibility and mechanical effectiveness. Animal studies confirm their biocompatibility and osteoconductivity. However, handling problems and the limited radiopacity of these cements currently preclude their clinical use.

Definition and classification of osteoporotic vertebral fracture

Vertebral fracture in osteoporosis has been critically analyzed. Prevalent fracture is defined by the morphometry on the spinal radiographs of lateral projection, following the visual semi-quantitative diagnosis. Incident fracture is defined by the changes in the values of morphometrical parameters on radiographs of two time points with a certain interval. Clinical vertebral fracture is not defined morphometrically, but acute clinical symptoms and semi-quantitative assessments are required for diagnosis. Discrimination of these three types of fracture is useful in the epidemiological studies and clinical trials for osteoporosis.

Vertebral fractures in osteoporosis: a new method for clinical assessment.

Vertebral fractures are the most common consequence of osteoporosis, and are an important risk factor for subsequent fractures. Patients with reduced bone mineral density (BMD) and vertebral fractures have significantly increased risk for future fractures, indicating great potential for the combined use of fracture assessment and BMD in risk evaluation. Despite the established importance of fractures, however, vertebral assessment is not typically performed in the clinical evaluation of patients at risk for osteoporosis. Radiographs are the accepted standard for assessment of fractures, but are rarely obtained in osteoporosis assessment for a variety of practical reasons, including cost, radiation dose, and the lack of office-based radiological facilities. Clinical assessment of fractures is difficult because most are asymptomatic. Consequently, this strong risk factor for osteoporotic fractures is often overlooked. High-resolution lateral spine images, obtained on advanced fan-beam dual X-ray absorptiometry (DXA) systems, provide a practical, low-radiation dose, point-of-care methodology for assessment of vertebral fractures, and have the potential to address this important clinical need. In this article, we review the importance of vertebral fractures and the methods of assessing them. We also review clinical data supporting the feasibility of visual evaluation of lateral spine images obtained using a fan-beam DXA system, and discuss the potential positive impact of this new methodology on clinical patient evaluation.

Early diagnosis and treatment of vertebral fractures in osteoporosis

Early diagnosis and treatment of vertebral fractures in osteoporosis

Hidden Costs of Vertebral Fractures in osteoporosis

Hidden Costs of Vertebral Fractures in osteoporosis

Drug therapy for vertebral fractures in osteoporosis: Evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy

The conventional belief is that osteopenia is the major cause of vertebral fractures and that drug therapy must induce a substantial increase in vertebral bone mineral density (BMD) before the vertebral fracture rate (VFR) is decreased. We hypothesized that the increased bone turnover in osteoporosis also is a major cause of vertebral fractures because of its adverse effects on the microarchitecture of the vertebrae and, thus, that normalization of bone turnover by antiresorptive drug therapy will decrease VFR substantially. This hypothesis is supported by our reanalysis of data from previous clinical trials with fluoride and with estrogen therapy in postmenopausal osteoporotic women. As evident from computer-generated three-dimensional graphic plots of data from osteoporotic women treated with placebo, VFR increased as bone turnover increased or as vertebral BMD decreased. Estrogen therapy decreased the bone turnover rate to normal and eliminated the relationship between VFR and bone turnover, whereas the inverse relationship with vertebral BMD persisted. In osteoporotic women treated with fluoride, VFR decreased as vertebral BMD increased, provided that patients with high (toxic) serum fluoride levels were not included in the comparison. Over the range of values in the data set, increased vertebral BMD and decreased bone turnover had approximately equal effects in decreasing VFR. Thus, both formation-stimulating and resorption-inhibiting drugs can substantially decrease VFR but do so by different mechanisms.

MRI findings on healing process of vertebral fracture in osteoporosis

The healing process of vertebral fracture was investigated in 37 senile osteoporotic patients on serial magnetic resonance imagings (MRIs), including enhancement study with gadolinium-diethylenetriamine pentaacetic acid (Gd- DTPA). The healing process was classified retrospectively into six categories in terms of the changes and recovery of T1 and T2 signal intensity and in terms of the local vascularity. Two types of damage loci were identified, and, in each type, three patterns of healing were noted. In the partial collapse type, the focus of damage in the fractured vertebral body was located near the cranial or caudal endplates; in the total collapse type, the focus was located at the center of the body. In each of these two types, fracture healing was smooth, belated, or resulted in nonunion. In the partial collapse type, vertebral fractures healed smoothly (smooth pattern) in 8 cases, belatedly (belated pattern) in 11, and resulted in nonunion (nonunion pattern) in 5. In the total collapse type, vertebral fractures healed smoothly (smooth pattern) in 6 cases, belatedly (belated pattern) in 4, and resulted in nonunion (nonunion pattern) in 3. The percent height of the anterior wall, central portion, and posterior wall was defined to allow accurate calculatation of the collapse of the fractured vertebral body. Chronological changes in the vertebral body height were investigated. Progressive collapse of the vertebral body was minimal in the smooth pattern cases, and most severe in the nonunion pattern cases. Statistical analysis indicated that prediction of the course of the fracture was difficult only with the height of the fractured vertebral body in acute phase. Enhancement study with Gd-DTPA showed that, in fractures with favorable prognosis, the ischemic area in the body tended to be smaller from the beginning, and restoration of vascularity was prompt. On the contrary, in fractures with unfavorable prognosis, the ischemic area was wider, and restoration of vascularity was poor.