Trabecular Bone Score in Patients With Chronic Glucocorticoid Therapy-Induced Osteoporosis Treated With Alendronate or Teriparatide.

OBJECTIVE: To determine the effect of alendronate (ALN) and teriparatide on trabecular bone score (TBS) in patients with glucocorticoid-induced osteoporosis. METHODS: Patients with chronic glucocorticoid therapy-induced osteoporosis (median 7.5 mg/day prednisone equivalent for ≥90 days) were randomized to receive oral ALN 10 mg/day (n = 214) or subcutaneous teriparatide 20 µg/day (n = 214) for 36 months; 118 patients in the ALN group and 123 patients in the teriparatide group completed treatment. Dual x-ray absorptiometry (DXA) results for 53 patients receiving ALN and 56 patients receiving teriparatide who had DXA scans with adequate resolution to perform TBS analysis and completed 36 months of therapy were blindly analyzed for TBS at baseline and 3, 6, 12, 18, 24, and 36 months. RESULTS: In teriparatide-treated patients, TBS was significantly increased at 18 months compared to baseline, and by 36 months had increased 3.7% (P < 0.05). In ALN-treated patients, there was not a significant change in TBS compared to baseline at any time point. Changes in lumbar spine bone mineral density (BMD) measured by DXA in the subgroup with TBS data were similar to BMD results in the overall study population. At 36 months, increases in lumbar spine BMD were 5.5% and 10.3% in patients treated with ALN and teriparatide, respectively. CONCLUSION: In patients with glucocorticoid-induced osteoporosis, both ALN and teriparatide increased lumbar spine BMD. However, trabecular bone score significantly increased with teriparatide but did not significantly change with ALN. The pathogenesis of glucocorticoid-induced osteoporosis is predominantly reduced bone formation. TBS may represent a sensitive measure to discriminate treatment effects of an anabolic versus an antiresorptive drug in glucocorticoid-induced osteoporosis.

Utility of spine bone mineral density in fracture prediction within FRAX.

Predicting individuals at risk for fracturing and modifying that risk are important in preventative health. Our aim was to quantify the impact of spine bone mineral density (BMD) on fracture risk prediction and determine the positive predictive value of fracture prediction using the lowest BMD value at the femoral neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of 15,033 women was performed, assessing the contribution of age, body mass index, number of clinical risk factors, T-score, and osteoporosis category to the presence of fracture. In patients whose lumbar spine T-scores are 1 or 2 osteoporosis categories lower than femoral neck, there is an approximately 30% increased risk of fracture compared with the femoral neck alone. For patients younger than 60 years, the odds ratio of having a fracture based on the presence of lumbar spine osteoporosis was greater than that based on femoral neck osteoporosis. Osteoporosis at the total hip correlated best with the presence of fracture. When using FRAX, we recommend that the 10-yr fracture prediction be adjusted when lumbar spine T-score is 1-2 osteoporosis categories lower than the femoral neck T-score or when lumbar spine T-score is ≥1 standard deviation less than femoral neck T-score.

Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).

Given the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.

International Society for Clinical Densitometry official positions: Asia-Pacific Region consensus.

The International Society for Clinical Densitometry (lSCD) is a nonprofit multidisciplinary international professional organization. The ISCD mission is to advance excellence in the assessment of skeletal health. To achieve this mission, the ISCD has conducted a number of Position Development Conferences over the past 10yr, bringing together international experts to review and create evidence-based position statements guiding clinicians involved in the area. The Asia-Pacific (AP) Panel of the ISCD was formed to give regional input to the ISCD from the AP Region and to oversee ISCD education and certification programs in the region. An AP Panel consensus meeting recently reviewed the most current Official Positions of the ISCD in view of the different population characteristics and health standards in the region. The reviewed position statements included those for bone testing by central and peripheral devices but did not include ISCD Official Positions on Vertebral Fracture Assessment or pediatric bone mineral density.

Position Development Conference of the International Society for Clinical Densitometry. Vancouver, BC, July 15-17, 2005.

Every 2 years the International Society for Clinical Densitometry (ISCD) organizes a position development conference at which a panel of experts reviews topics of interest in the field of bone densitometry and proposes Official Positions of the ISCD. In July 2005, the most recent conference was held in Vancouver, Canada, during which 4 topics were discussed: (1) Cross-calibration of dual energy x-ray absorptiometry (DXA) systems, (2) Vertebral fracture assessment, (3) World Health Organization (WHO) classification of bone density for populations other than postmenopausal women, and (4) WHO classification for varying skeletal sites. The Official Positions reached at this conference enumerated in this report have been published in The Journal of Clinical Densitometry, and can be found at www.iscd.org.

Official positions of the International Society for Clinical Densitometry and Executive Summary of the 2005 Position Development Conference.

The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every two years for the purpose of making recommendations on clinically relevant issues in bone densitometry. Topics for consideration are developed by the ISCD Scientific Advisory Committee and the PDC Steering Committee. Clinically relevant questions related to each topic area are assigned to subcommittees for a comprehensive medical literature review and presentation of a report to an international panel of experts. The expert panel includes representatives of the American Society for Bone and Mineral Research (ASBMR) and the International Osteoporosis Foundation (IOF). The recommendations of the PDC expert panel are evaluated by the ISCD Board of Directors, and those that are approved become Official Positions of the ISCD. The Official Positions have subsequently been endorsed by the ASBMR and IOF. The most recent PDC was held July 15-17, 2005, in Vancouver, BC, Canada. Topics considered included technical standardization, vertebral fracture assessment, and application of the 1994 World Health Organization (WHO) criteria to various skeletal sites and to populations other than postmenopausal white women. This report describes the methodology of the 2005 PDC and presents a summary of all ISCD Official Positions.

Cross-calibration and minimum precision standards for dual-energy X-ray absorptiometry: the 2005 ISCD Official Positions.

The International Society for Clinical Densitometry (ISCD) Committee on Standards of Bone Measurement (CSBM) consists of experts in technical aspects of bone densitometry. The CSBM recently reviewed the scientific literature on cross-calibration and precision assessment. A report with recommendations was presented at the 2005 ISCD Position Development Conference (PDC). Based on a thorough review of the data by the ISCD Expert Panel during the conference, the ISCD adopted Official Positions with respect to (1) cross-calibration when changing or replacing hardware; (2) the approach to cross-calibration when an entire system is changed to one made by either the same or a different manufacturer; (3) when no cross-calibration study or bone mineral density (BMD) comparison is done between facilities; and (4) the minimum acceptable precision for an individual technologist. We present here the ISCD Official Positions on these topics that were established as a result of the 2005 PDC, together with the associated rationales and supportive evidence.

Review of treatment modalities for postmenopausal osteoporosis.

This review summarizes and updates data presented at recent annual Southern Medical Association conferences on postmenopausal osteoporosis. As part of any osteoporosis treatment program, it is important to maintain adequate calcium and 25-hydroxyvitamin D levels either through diet or supplementation. Among the available pharmacologic therapies, the bisphosphonates alendronate and risedronate have demonstrated the most robust fracture risk reductions-approximately 40 to 50% reduction in vertebral fracture risk, 30 to 40% in nonvertebral fracture risk, and 40 to 60% in hip fracture risk. Ibandronate, a new bisphosphonate, has demonstrated efficacy in reducing vertebral fracture risk. Salmon calcitonin nasal spray and raloxifene demonstrated significant reductions in vertebral fracture risk in pivotal studies. Teriparatide significantly reduced vertebral and nonvertebral fracture risk. Drugs on the horizon include strontium ranelate, which has been shown to reduce vertebral and nonvertebral fracture risk, and zoledronic acid, an injectable bisphosphonate that increased bone density with once-yearly administration.

Treatment of low bone mass in premenopausal women: when may it be appropriate?

The diagnosis and treatment of osteoporosis in postmenopausal women has been well defined. Criteria for making a diagnosis using bone density testing has been established and widely disseminated. However, the definition established by the World Health Organization for osteoporosis cannot be used for other populations such as premenopausal women without further study. Measuring bone mass in premenopausal women should be done infrequently and only if specific and significant risk factors are present. Premenopausal women have a low risk for fracturing but women with low bone mass are at a greater risk for developing fractures before and after menopause. The major reason for low bone mass is the failure to reach peak bone mass because of genetic influences, although some environ-mental factors may also play a role. Hormonal therapy for hypogonadism, treatment of diseases such as hyperpara-thyroidism, and keeping medications with detrimental effects on bone to a minimum are important components of treatment. Pharmacologic treatment of low bone mass in premenopausal women has not been well studied although on rare occasions it may be appropriate in women with low bone mass, defined as a Z score of -2 or less, and the presence of other diseases or risk factors. Caution is urged because of the unknown effects of treatment in this population. Further study of the implications of low bone mass and the effects of treatment in this group of women is needed.

Official positions of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) has convened two Position Development Conferences at which a panel of experts agreed on recommendations for performance and clinical applications of bone density testing. These recommendation were reviewed by the ISCD Board of Directors, and those approved by the board are now official positions of the ISCD. These include (1) indications for bone density testing, (2) reference databases for T-scores, (3) standards for performing central dual-energy X-ray absorptiometry (DXA) for diagnosis, (4) interpretation of peripheral bone density results, (5) diagnosis of osteoporosis in postmenopausal women, (6) diagnosis of osteoporosis in men, (7) diagnosis in premenopausal women, (8) diagnosis in children, (9) indications and interpretation for serial bone mass measurement, (10) technical standards for phantom scanning and calibration, (11) technical standards for cross-calibration of DXAsystems, and (12) standards for reporting of bone density results including correct nomenclature and preferred number of decimal digits.

Standards and guidelines for performing central dual-energy x-ray absorptiometry in premenopausal women, men, and children.

The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

Position Development Conference.

In a series of three published articles, the International Society for Clinical Densitometry has recorded the findings reached by an expert panel at the ISCD Position Development Conference held in July 2001. The key elements of those papers have been reviewed in this executive summary. It should be emphasized that the ISCD recommendations are not meant to serve as rigid guidelines or to replace clinical judgment. The recommendations will be reviewed and updated periodically as more data become available. A second Position Development Conference will be held in July 2003 in Cincinnati, OH. For information, visit the ISCD web site: http://www.iscd.org/.

Executive summary International Society for Clinical Densitometry position development conference Denver, Colorado July 20-22, 2001.

Bone densitometry is routinely used to assess the skeleton in patients who have diseases or conditions that can cause low bone mass. However, there are some areas of controversy related to the interpretation of bone densitometry results. To address these issues, the International Society for Clinical Densitometry (ISCD) convened a Position Development Conference in Denver, Colorado, July 20-22, 2001. The ISCD is a not-for-profit multidisciplinary society whose main mission is to promote quality in the performance and interpretation of bone densitometry examinations.

Position statements of the International Society for Clinical Densitometry: methodology.

Given the need for authoritative positions in areas of controversy in the field of bone densitometry, the International Society for Clinical Densitometry (ISCD) convened a Position Development Conference in Denver, CO, USA, in July 2001. Four general areas were selected on the basis of clinical importance and likelihood of reaching agreement. These areas were discussed at length prior to the conference by the Scientific Advisory Committee of the ISCD and presented to a panel of experts at the conference. The four areas included discussions of (1). the regions of interest of central dual X-ray densitometry (DXA), (2). the criteria by which a densitometric diagnosis of osteoporosis can be made in men and non-Caucasian women, (3). the role of serial BMD measurements in patient management, and (4). the standards by which bone mass measurements at peripheral sites should be used in the diagnosis of osteoporosis. Details of the methodology used at the conference are discussed. The following papers explain the results of the discussions and describe the official ISCD positions.