S. T. Harris

Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty

Abstract: Vertebral fracture is the most common complication of osteoporosis. It results in significant mortality and morbidity, including prolonged and intractable pain in a minority of patients. Vertebroplasty and kyphoplasty, procedures that involve percutaneous injection of bone cement into a collapsed vertebra, have recently been introduced for treatment of osteoporotic patients who have prolonged pain (several weeks or longer) following vertebral fracture. To determine the details of the procedures and to gather information on their safety and efficacy, we performed a MEDLINE search using the terms “vertebroplasty” and “kyphoplasty.” We reviewed reports of these procedures in patients with osteoporosis. We supplemented the articles found with other papers known to the authors and with presentations at national meetings. Randomized trials of vertebroplasty and kyphoplasty have not been reported. Case reports suggest that these procedures are associated with pain relief in 67% to 100% of cases. Short-term complications, mainly the result of extravasation of cement, include increased pain and damage from heat or pressure to the spinal cord or nerve roots. Proper patient selection and good technique should minimize complications, but rarely, decompressive surgery is needed. Long-term benefits have not yet been shown, but potentially include prevention of recurrent pain at the treated level(s) with both procedures, and, with kyphoplasty, reversal of height loss and spinal deformity, an improved level of function, and avoidance of chronic pain and restriction of internal organs. Possible long-term complications, again not fully evaluated, include local acceleration of bone resorption caused by the treatment itself or by foreign-body reaction at the cement–bone interface, and increased risk of fracture in treated or adjacent vertebrae through changes in mechanical forces. Controlled trials are needed to determine both short-term and long-term safety and efficacy of vertebroplasty and kyphoplasty. Both procedures may be useful for osteoporotic patients who have prolonged pain following acute vertebral fracture. Until there is conclusive evidence for efficacy and long-term safety, these procedures should be done only in carefully selected patients, only by experienced operators with appropriate high-quality imaging equipment, and ideally at centers that are participating in controlled trials.

In Vivo Assessment of Architecture and Micro-Finite Element Analysis Derived Indices of Mechanical Properties of Trabecular Bone in the Radius

Abstract: Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (μFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n= 22, mean age 58 ± 7 years) and (II) postmenopausal women with spine or femur BMD −1 SD to −2.5 SD below young normal (n= 37, mean age 62 ± 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young’s moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with μFE modeling in vivo in the study of osteoporosis.

Factors affecting broadband ultrasound attenuation results of the calcaneus using a gel-coupled quantitative ultrasound scanning system.

Abstract: This study aimed to assess the factors that may influence the distribution and description of broadband ultrasound attenuation (BUA) and to identify specific criteria for diagnostic consideration when collecting BUA reference data. Two hundred Caucasian women (aged 20–79 years) without a history of atraumatic fractures or medicines known to affect bone metabolism were selected for this study. Medical and menstrual history, medication usage, family history of osteoporosis (FHO), physical activity, activities of daily living (ADL), dietary calcium intake, as well as smoking and alcohol consumption were obtained. Broadband ultrasound attenuation (BUA, dB/MHz) was determined in the right foot using a new gel-coupled ultrasound system. BUA was significantly associated with age (p<0.001), body weight (p<0.001), level of physical activity (p = 0.024) and dietary calcium intake (p= 0.023). Smoking, alcohol and coffee consumption and ADL were not associated with BUA (p>0.05). There were no differences in BUA (p>0.05) between those women who reported taking medications or had diseases (known to not affect bone metabolism), were using contraceptives, taking vitamin/mineral supplements and/or had traumatic fractures and their counterparts who did not report these characteristics. Premenopausal women with a FHO had significantly lower BUA values compared with those without a FHO (p= 0.013). When those participants with a FHO were removed from the sample, the peak BUA value was 1.1–4.4% higher and the variability (SD) was reduced by about 3.3–9.3% depending on which age range was used to define the peak BUA value. Consequently, an additional 4.5% of the population were classified as having a T-score <−2. Our results suggest that the impact on BUA of risk factors such as a FHO, body weight, physical activity and dietary calcium intake is similar to that on bone mineral density obtained by dual-energy X-ray absorptiometry (DXA), and thus provides further information on the comparability of quantitative ultrasound and DXA for assessment of risk of fracture. The criteria for calculating the T-score need further study to determine whether young adults with FHO should be included and what cutoff age range should be used in collecting peak values of quantitative ultrasound parameters.

Short-term effect of alendronate on bone mass and bone remodeling in postmenopausal women

The short-term dose-response relationship between treatment with the bisphosphonate alendronate, biochemical markers of bone turnover, and changes in lumbar spine bone mineral density (BMD) over 9 months was assessed using a double-masked controlled study design in 65 postmenopausal women (mean age 51.6 years, mean 1.5 years since last menses) receiving 5, 20, 40 mg of alendronate or placebo for 6 weeks. After 6 weeks of alendronate, serum calcium phosphate and osteocalcin decreased, and intact parathyroid hormone increased significantly in dose-dependent fashions in the alendronate-treated groups (T) compared with placebo (P). Generally similar changes (decreases) were noted in 24-h urinary calcium and pyridinoline (deoxy- and hydroxylysl pyridoline); by 30 weeks post-treatment no significant changes from baseline or between T and P were noted. Lumbar BMD by dual-energy X-ray absorptiometry demonstrated a dose-dependent response over 9 months (median % change ±SD: −1.2±0.9 for 5 mg T, +0.7±0.8 for 20 mg T*, +1.2±1.1 for 40 mg T*;*p<0.01 vs P). Alendronate was generally well tolerated over all dosages. These data demonstrate that short-term (6 weeks) oral alendronate treatment (5–40 mg daily) is well tolerated and effective in (reversibly) decreasing biochemical markers of bone turnover in early postmenopausal women, and in stabilizing spinal BMD over 9 months. Longer-term treatment with larger clinical populations is indicated to define more fully the potential efficacy and safety of chronic alendronate therapy.

Bisphosphonates for the Treatment of Postmenopausal Osteoporosis: Clinical Studies of Etidronate and Alendronate

Several large, prospective, controlled trials have demonstrated that bisphosphonates such as etidronate and alendronate are effective and generally safe for the treatment of postmenopausal osteoporosis. The results of these trials show a remarkable degree of consistency and indicate that long-term bisphosphonate therapy significantly increases BMD of the spine and of other skeletal sites, reduces the risk of vertebral and nonvertebral fractures, and generally is safe and well tolerated by patients. Data supporting the use of risedronate for the treatment of postmenopausal osteoporosis are presented in an accompanying article.

Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis.

The number needed to treat is a valuable metric to determine the benefit of therapy, but it must be viewed against the respective number needed to harm. Denosumab and teriparatide (TPTD) have proven antifracture efficacy at vertebral and nonvertebral sites, whereas raloxifene has proven antifracture efficacy at the spine only. Denosumab use has been associated with a small, yet statistically significant, increased incidence of eczema and serious cellulitis. Raloxifene use has been associated with statistically significant increases in the risk of venous thromboembolism and possibly deadly stroke, although not an increase in total strokes. No significant, nontransient adverse events have been reported with TPTD use. When used for the treatment of postmenopausal osteoporosis, denosumab, raloxifene, and TPTD all generally have favorable risk-to-benefit profiles, but therapy-specific contraindications necessitate thoughtful consideration of all available clinical information and individualization of treatment decisions.

Western Osteoporosis Alliance Clinical Practice Series: Evaluating the Balance of Benefits and Risks of Long-Term Osteoporosis Therapies

Osteoporosis is a chronic disease that requires life-long strategies to reduce fracture risk. Few trials have investigated the balance of benefits and risk with long-term use of osteoporosis therapies, and fewer still have investigated the consequences of treatment discontinuation. The best available evidence suggests that up to 10 years of treatment with an oral bisphosphonate maintains the degree of fracture risk reduction observed in the 3-year registration trials. With denosumab, 10 years of therapy appears to provide fracture risk reduction similar to or better than that observed in the 3-year registration trial. Available data suggest an increasing but low risk of fractures with atypical features with increasing duration of bisphosphonate therapy. Published data linking duration of therapy to osteonecrosis of the jaw are lacking for bisphosphonates and denosumab. Other side effects associated with denosumab or bisphosphonates do not appear to be related to therapy duration. The antifracture benefits of long-term therapy with bisphosphonates and denosumab in appropriately selected patients outweigh the low risk of serious side effects.