The Vertebral Fracture Cascade: Etiology and Clinical Implications.

A vertebral fracture is a marker of bone fragility and is associated with a downward spiral of recurrent fractures known as the vertebral fracture cascade. Etiology of this unfortunate cascade includes bone and muscle loss from immobility, changes in spinal mechanics causing increased loading on adjacent vertebrae, and the development of an increased thoracic kyphosis (hyperkyphosis [HK]). Degenerative disc disease, common in osteoporotic patients, can also cause HK. HK of any etiology has been associated with decreased thoracic extensor muscle strength, unstable gait, increased body sway, decreased physical and pulmonary functions, chronic pain, and increased spinal loads contributing to the vertebral fracture cascade. Preventing this downward spiral requires a multidisciplinary approach that includes early identification, consideration of pharmacologic treatment, early mobilization of the fracture patient, appropriate exercise, and back protection. Exercise should include weight-bearing and muscle-strengthening activities, but caution is needed to avoid undue stress on the back. Physical therapy can be particularly helpful by teaching the patient how to safely perform daily activities and can assist the patient in establishing a safe exercise program that avoids flexion but promotes back extension and weight-bearing activities. Hopefully, these measures will decrease pain, prevent falls, improve posture, prevent additional bone and muscle loss, and potentially abort the devastating downward spiral of the vertebral fracture cascade.

Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD.

There have been many scientific advances in fracture risk prediction beyond bone density. The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of dual-energy X-ray absorptiometry beyond measurement of bone mineral density for fracture risk assessment, including trabecular bone score and hip geometry measures. Previously, no guidelines for nonbone mineral density DXA measures existed. Furthermore, there have been advances in the analysis of quantitative computed tomography (QCT) including finite element analysis, QCT of the hip, DXA-equivalent hip measurements, and opportunistic screening that were not included in the previous ISCD positions. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three task forces were created and asked to conduct comprehensive literature reviews to address specific questions. The task forces included participants from many countries and a variety of interests including academic institutions and private health care delivery organizations. Representatives from industry participated as consultants to the task forces. Task force reports with proposed position statements were then presented to an international panel of experts with backgrounds in bone densitometry. The PDC was held in Chicago, Illinois, USA, contemporaneously with the Annual Meeting of the ISCD, February 26 through February 28, 2015. This Executive Summary describes the methodology of the 2015 PDC on advanced measures from DXA and QCT and summarizes the approved official positions. Six separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the task forces addressed.

Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 1: Hip Geometry.

Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry is the current imaging procedure of choice to assess fracture risk. However, BMD is only one of the factors that explain bone strength or resistance to fracture. Other factors include bone microarchitecture and macroarchitecture. We now have the ability to assess some of these non-BMD parameters from a dual-energy X-ray absorptiometry image. Available measurements include various measurements of hip geometry including hip structural analysis, hip axis length, and neck-shaft angle. At the 2015 Position Development Conference, the International Society of Clinical Densitometry established official positions for the clinical utility of measurements of hip geometry. We present the official positions approved by an expert panel after careful review of the recommendations and evidence prepared by an independent task force. Each question addressed by the task force is presented followed by the official position with the associated medical evidence and rationale.

Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score.

Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis and management of osteoporosis. However, BMD explains only 60%-80% of bone strength, and a number of skeletal features other than BMD contribute to bone strength and fracture risk. Advanced imaging modalities can assess some of these skeletal features, but compared to standard DXA, these techniques have higher costs and limited accessibility. A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. To this end, trabecular bone score (TBS), a gray-level textural index derived from the lumbar spine DXA image, has been investigated. The purpose of this International Society for Clinical Densitometry task force was to review the evidence and develop recommendations on how to incorporate TBS in clinical practice. Clinical applications of TBS for fracture risk assessment, treatment initiation, monitoring of treatment, and use of TBS in special conditions related to greater fracture risk, were addressed. We present the official positions approved by an expert panel following careful review of the recommendations and evidence presented by the TBS task force.

Measurement of Hip Geometry-Technical Background.

Conventional dual-energy X-ray absorptiometry images display a digital projection of the inorganic mineral mass in a scanned region. Bone mineral density software generates an average of the pixels within one or more regions. Although not used in the conventional analysis, the images also contain dimensional information limited to the plane of the image. The hip structure analysis method and that of the similar GE, Madison, WI, algorithm Advanced Hip Analysis use both the dimensional information and the mineral mass data to compute the types of dimensional properties (i.e., geometry) that are used to evaluate mechanical strength in engineering analyses. This article describes the hip structure analysis method and a somewhat cruder geometry approximation that does not require a reanalysis of the image. Limitations of the methods are discussed.

Official Positions for FRAX® clinical regarding rheumatoid arthritis from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Rheumatoid arthritis is the only secondary cause of osteoporosis that is considered independent of bone density in the FRAX(®) algorithm. Although input for rheumatoid arthritis in FRAX(®) is a dichotomous variable, intuitively, one would expect that more severe or active disease would be associated with a greater risk for fracture. We reviewed the literature to determine if specific disease parameters or medication use could be used to better characterize fracture risk in individuals with rheumatoid arthritis. Although many studies document a correlation between various parameters of disease activity or severity and decreased bone density, fewer have associated these variables with fracture risk. We reviewed these studies in detail and concluded that disability measures such as HAQ (Health Assessment Questionnaire) and functional class do correlate with clinical fractures but not morphometric vertebral fractures. One large study found a strong correlation with duration of disease and fracture risk but additional studies are needed to confirm this. There was little evidence to correlate other measures of disease such as DAS (disease activity score), VAS (visual analogue scale), acute phase reactants, use of non-glucocorticoid medications and increased fracture risk. We concluded that FRAX(®) calculations may underestimate fracture probability in patients with impaired functional status from rheumatoid arthritis but that this could not be quantified at this time. At this time, other disease measures cannot be used for fracture prediction. However only a few, mostly small studies addressed other disease parameters and further research is needed. Additional questions for future research are suggested.

Algorithm for the management of osteoporosis.

Osteoporosis is a common skeletal disease that weakens bones and increases the risk of fractures. It affects about one half of women over the age of 60, and one third of older men. With appropriate care, osteoporosis can be prevented; and when present, it can be easily diagnosed and managed. Unfortunately, many patients with osteoporosis are not recognized or treated, even after sustaining a low-trauma fracture. Even when treatment is initiated, patients may not take medication correctly, regularly, or for a sufficient amount of time to receive the benefit of fracture risk reduction. Efforts to improve compliance and treatment outcomes include longer dosing intervals and parenteral administration. Clinical practice guidelines for the prevention and treatment of osteoporosis have been developed by the National Osteoporosis Foundation (NOF) but may not be fully utilized by clinicians who must deal with numerous healthcare priorities. We present an algorithm to help streamline the work of busy clinicians so they can efficiently provide state-of-the-art care to patients with osteoporosis.

Vertebral Fracture Assessment: the 2007 ISCD Official Positions.

Vertebral fracture assessment (VFA) is an established, low radiation method for detection of prevalent vertebral fractures. Vertebral fractures are usually not recognized clinically at the time of their occurrence, but their presence indicates a substantial risk for subsequent fractures independent of bone mineral density. Significant evidence supporting VFA use for many post-menopausal women and older men has accumulated since the last ISCD Official Position Statement on VFA was published. The International Society for Clinical Densitometry considered the following issues at the 2007 Position Development Conference: (1) What are appropriate indications for Vertebral Fracture Assessment; (2) What is the most appropriate method of vertebral fracture detection with VFA; (3) What is the sensitivity and specificity for detection of vertebral fractures with this method; (4) When should additional spine imaging be performed following a VFA; and (5) What are the reporting obligations for those interpreting VFA images?

Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density.

OBJECTIVE: Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis. Supplemental calcium is also generally recommended. This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment. METHODS: This 2-year, randomized, double-blind, multicenter trial enrolled healthy, postmenopausal women with low bone mineral density (BMD). Patients with a dietary calcium intake > or = 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo, alendronate 10 mg/elemental calcium 1000 mg, or alendronate-placebo/calcium 1000 mg (2:2:1). Endpoints included BMD, bone turnover markers (BTMs), and adverse events. RESULTS: Randomized patients (N = 701) were an average of 20.4 years postmenopausal. After 24 months, increases in lumbar spine BMD differed significantly between patients receiving calcium alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium (6.0%) (p < 0.001). Significant differences were also seen at the trochanter and femoral neck (p < 0.001). BTMs were significantly lower with alendronate-containing treatments than calcium alone (p < 0.001). Addition of calcium supplementation to alendronate did not significantly increase BMD compared to alendronate alone (p = 0.29 to 0.97), but did result in a statistically significant, though small, additional reduction in urinary NTx. Adverse events were similar among treatment groups. Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30%, although discontinuation rates were similar among treatment groups. CONCLUSIONS: In postmenopausal women with a daily intake of > or =800 mg calcium and 400 IU vitamin D, 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg resulted in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone. Addition of supplemental calcium to alendronate treatment had no effect on BMD and resulted in a small, though statistically significant, additional reduction in NTx.

Vertebral fracture assessment: the 2005 ISCD Official Positions.

Vertebral Fracture Assessment (VFA) is a low radiation method for imaging the thoraco-lumbar spine using bone densitometers. VFA can easily be performed at the time of bone mineral density (BMD) measurement, allowing integration of BMD and vertebral fracture information into clinical patient care. As VFA is a relatively new procedure, it has received limited study and heretofore has not had widespread clinical application. Consequently, the International Society for Clinical Densitometry (ISCD) considered the following VFA issues at the 2005 Position Development Conference: (1) indications for VFA; (2) methodology for the diagnosis of vertebral fractures using VFA; and (3) indications for additional imaging after VFA. The ISCD Official Positions with respect to the above issues, as well as the rationale and evidence used to derive these positions, are presented here.

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

UNLABELLED: Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.

Hip fracture patients are not treated for osteoporosis: a call to action.

OBJECTIVE: To determine whether hip fracture patients, a group at very high risk for additional fragility fractures, are being evaluated and treated effectively for osteoporosis. METHODS: Clinical and bone densitometry (dual x-ray absorptiometry [DXA]) records were reviewed in hip fracture patients at 4 Midwestern US health systems to determine the frequency of DXA use, calcium and vitamin D supplementation, and antiresorptive drug treatment. RESULTS: DXA was performed at the 4 study sites in only 12%, 12%, 13%, and 24% of patients, respectively. Calcium and vitamin D supplements were prescribed in 27%, 1%, 3%, and 25% of the patients at the 4 study sites. Antiresorptive drugs were prescribed in 26%, 12%, 7%, and 37% of the patients with only 2-10% receiving a bisphosphonate. CONCLUSION: Reducing osteoporotic fractures will require more effective approaches to managing hip fracture patients and other high-risk populations.