Dieter Felsenberg

Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research

ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force.

Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis

Oral daily (2.5 mg) and intermittent ibandronate (between‐dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate.

Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-Year Results From the MOBILE Study

Once‐monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3‐year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year.

Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Epidemiology, treatment and costs of osteoporosis in Germany—the BoneEVA Study

IntroductionIn Germany, accurate data on the prevalence and treatment of osteoporosis, as well as the cost of this illness, are not available. The aim of this study is to give a valid estimation of these items for the year 2003.MethodsRoutine data from a German sickness fund covering 1.5 million beneficiaries and billing data for outpatient visits were used to obtain estimates of prevalence for osteoporosis. Claims data for patients with osteoporosis (M80, M81) or an osteoporosis-related fracture diagnosis (S22, S32, S42, S52, S72, S82) or treatment with anti-osteoporosis drugs were examined. Costs were calculated from the perspective of the German health insurance system and the German nursing care insurance system, respectively. Only direct costs of osteoporosis were considered.ResultsIn 2003, 7.8 million Germans (6.5 million women) were affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporosis drug. The total direct costs attributable to osteoporosis amounted to €5.4 billion.ConclusionThis study confirms that osteoporosis is underdiagnosed, undertreated and imposes a considerable economic burden on the health system in Germany. Effective strategies for the prevention and management of this disease are needed.

Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of a five-year, randomized, placebo-controlled trial.

OBJECTIVE This study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5-year, double-blind, placebo-controlled trial. METHODS A total of 5,091 postmenopausal women with osteoporosis were randomized to receive either strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy criterion was the incidence of nonvertebral fractures. In addition, incidence of hip fractures was assessed, by post hoc analysis, in the subset of 1,128 patients who were at high risk of fractures (age 74 years or older with lumbar spine and femoral neck bone mineral density T scores -2.4 or less). The incidence of new vertebral fractures was assessed, using the semiquantitative method described by Genant, in the 3,646 patients in whom spinal radiography (a nonmandatory procedure) was performed during the course of the study. Fracture data were analyzed using the Kaplan-Meier survival method. RESULTS Of the 5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of nonvertebral fracture was reduced by 15% in the strontium ranelate group compared with the placebo group (relative risk 0.85 [95% confidence interval 0.73-0.99]). The risk of hip fracture was decreased by 43% (relative risk 0.57 [95% confidence interval 0.33-0.97]), and the risk of vertebral fracture was decreased by 24% (relative risk 0.76 [95% CI 0.65-0.88]) in the strontium ranelate group. After 5 years, the safety profile of strontium ranelate remained unchanged compared with the 3-year findings. CONCLUSION Our findings indicate that treatment of postmenopausal osteoporosis with strontium ranelate results in a sustained reduction in the incidence of osteoporotic nonvertebral fractures, including hip fractures, and vertebral fractures over 5 years.

The European Spine Phantom: a tool for standardization and quality control in spinal bone mineral measurements by DXA and QCT

The lack of standardization in bone mineral measurements of the lumbar spine and other skeletal sites is generally recognized as an important and unresolved issue. We report and discuss efforts at standardization and cross-calibration of DXA and QCT equipment. We have designed and tested a geometrically defined, semi-anthropomorphic phantom, the European Spine Phantom (ESP). It contains a spine insert consisting of three vertebrae of increasing bone mineral densities and thicknesses of cortical structures; the respective parameters are given in tabular form for the final phantom design. Results for cross-calibration with the ESP compare well with patient results. Measurements on the first 30 phantoms confirmed that the ESP can be manufactured with a variation of about 1%. We conclude that the ESP is suitable for daily quality assurance, cross-calibration of instruments and universal standardization. The ESP was used to establish standardized BMD (sBMD) units for DXA equipment going into effect in late 1995. Its acceptance by manufacturers as a calibration standard for DXA and QCT measurements appears imminent.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Pagets disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.

Treatment of chronic lower back pain with lumbar extension and whole-body vibration exercise: a randomized controlled trial.

Study Design. A randomized controlled trial with a 6-month follow-up period was conducted. Objective. To compare lumbar extension exercise and whole-body vibration exercise for chronic lower back pain. Summary of Background Data. Chronic lower back pain involves muscular as well as connective and neural systems. Different types of physiotherapy are applied for its treatment. Industrial vibration is regarded as a risk factor. Recently, vibration exercise has been developed as a new type of physiotherapy. It is thought to activate muscles via reflexes. Methods. In this study, 60 patients with chronic lower back pain devoid of “specific” spine diseases, who had a mean age of 51.7 years and a pain history of 13.1 years, practiced either isodynamic lumbar extension or vibration exercise for 3 months. Outcome measures were lumbar extension torque, pain sensation (visual analog scale), and pain-related disability (pain disability index). Results. A significant and comparable reduction in pain sensation and pain-related disability was observed in both groups. Lumbar extension torque increased significantly in the vibration exercise group (30.1 Nm/kg), but significantly more in the lumbar extension group (+59.2 Nm/kg; SEM 10.2;P < 0.05). No correlation was found between gain in lumbar torque and pain relief or pain-related disability (P > 0.2). Conclusions. The current data indicate that poor lumbar muscle force probably is not the exclusive cause of chronic lower back pain. Different types of exercise therapy tend to yield comparable results. Interestingly, well-controlled vibration may be the cure rather than the cause of lower back pain.