Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contained a mistake.

Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contains some typos in Figs. 2, 3, 4, and Supplemental Fig. 1. The corrected figures are given below.

Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates.

Transitioning postmenopausal women with osteoporosis from a bisphosphonate to denosumab appears to be safe and more effective at improving BMD than continuing treatment with a bisphosphonate. INTRODUCTION: We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates. METHODS: Patients received 60 mg denosumab once every 6 months or a bisphosphonate (oral alendronate, risedronate, ibandronate, or intravenous zoledronic acid). Endpoints were change from baseline in lumbar spine, total hip, femoral neck, and 1/3 radius BMD at month 12, change from baseline in serum CTX-1 and P1NP, and incidence of adverse events. RESULTS: A total of 2850 randomized patients (1424 bisphosphonate:1426 denosumab) were included in the analysis. Percentage change in BMD was significantly greater (p < 0.001) for denosumab vs. bisphosphonate at each skeletal site; differences in BMD changes ranged from 0.6 to 2.0%. Percentage decrease in serum CTX-1 and P1NP was significantly greater (p < 0.0001) for denosumab vs. bisphosphonate at months 1, 6, and 12; in the denosumab group only, percentage change in serum CTX-1 at month 1 was significantly correlated with percentage change in lumbar spine and total hip BMD at month 12. The incidences of adverse events were similar between treatment groups. Three patients (one bisphosphonate and two denosumab) had atypical femoral fractures, all from the denosumab vs. zoledronic acid study. CONCLUSION: Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate. CLINICAL TRIALS REGISTRATION: NCT00377819, NCT00919711, NCT00936897, NCT01732770.

Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

PURPOSE: Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture. METHODS: Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463). RESULTS: After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11). CONCLUSIONS: Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Observations following discontinuation of long-term denosumab therapy.

Stopping denosumab after 8 years of continued treatment was associated with bone loss during a 1-year observation study in patients who were not prescribed osteoporosis treatment. Bone loss was attenuated in patients who began another osteoporosis therapy. Treatment to prevent bone loss upon stopping denosumab should be considered. INTRODUCTION: This study aimed to understand osteoporosis management strategies during a 1-year observational follow-up after up to 8 years of denosumab treatment in a phase 2 study. METHODS: During the observational year, patients received osteoporosis management at the discretion of their physician and returned to the clinic for BMD assessment and completion of an osteoporosis management questionnaire. Incidence of serious adverse events and fractures was collected. Analyses were descriptive. RESULTS: Of 138 eligible patients, 82 enrolled in and completed the observation study. Most (65 [79%]) did not receive prescription osteoporosis medication, with "my doctor felt I no longer needed a medication" being the most common reason (23 [35%]). Of the 17 patients who took osteoporosis medications, 8 discontinued therapy during the observation study. In patients treated with denosumab for 8 years (N = 52), BMD decreased during the 1-year observation study (6.7% [lumbar spine], 6.6% [total hip]). Those who took osteoporosis medication during the observation study showed a smaller decline in BMD than those who did not. No new safety concerns were identified. Eight patients (9.8%), all of whom had at least one predisposing risk factor, experienced 17 fractures. This included seven patients who experienced one or more vertebral fractures. CONCLUSIONS: Consistent with denosumab's mechanism of action, treatment cessation led to reversal of the drug's effect on BMD and perhaps fracture risk. For patients who took osteoporosis therapy, bone loss was attenuated. For patients at high fracture risk, switching to another osteoporosis therapy if denosumab is discontinued seems appropriate.

Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study.

UNLABELLED: The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated. INTRODUCTION: ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD ( ClinicalTrials.gov NCT00112437). METHODS: In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients (n = 117) received open-label ODN 50 mg QW plus weekly vitamin D3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration. RESULTS: Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately -50 % (uNTx/Cr) and -45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported. CONCLUSIONS: Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated.

Fracture incidence in a large cohort of men age 30 years and older with osteoporosis.

UNLABELLED: In this large retrospective study of men with presumed osteoporosis, we estimate the rate of osteoporosis-related fractures in men age ≥30 years. Our results suggest that spine and hip fractures continue to be a considerable disease burden for osteoporotic men of all ages. INTRODUCTION: The purposes of this study were to describe a cohort of men with presumed osteoporosis and estimate the incidence rates of fractures by age. METHODS: Using US administrative claims data, we identified 43,813 men ≥30 years old with an osteoporosis diagnosis or use of an osteoporosis medication. Men were followed for a minimum of 12 months after diagnosis or treatment of osteoporosis (index date), until the earliest of fracture (hip, spine, pelvis, distal femur, humerus, wrist, forearm), disenrollment, or study end date. RESULTS: During the study period, there were 3834 first fractures following the index date and 3303 fractures in the 6-month period prior to the diagnosis/treatment of osteoporosis. Incidence rates of osteoporosis-related fracture, estimated from the index date onward, increased with age, although did not significantly differ from one another in younger age groups (30-49 and 50-64 years). Spine fractures had the highest incidence rate in men across all age groups, increasing from 10.8 per 100,000 person-years (p-yrs) (95% confidence interval (CI) 9.1, 12.7), 12.2 per 100,000 p-yrs (95% CI 11.2, 13.3), and 15.3 per 100,000 p-yrs (95% CI 13.8, 16.9) in men 30-49, 50-64, and 65-74 years to 33.4 per 100,000 p-yrs (95% CI 31.5, 35.4) in men ≥75 years. Hip fractures were the second most common, with the incidence rate reaching 16.2 per 100,000 (95% CI 14.9, 17.6) in the ≥75-year group. CONCLUSION: These incidence rates suggest that spine and hip fractures are a considerable disease burden for men of all ages diagnosed and/or treated for osteoporosis.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years.

UNLABELLED: Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION: This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS: Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS: For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS: Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

PINP as a biological response marker during teriparatide treatment for osteoporosis.

Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.

Prevalence of renal impairment among osteoporotic women in the USA, NHANES 2005-2008: is treatment with bisphosphonates an option?

UNLABELLED: Bisphosphonates are the first-line treatment for osteoporotic (OP) women; however, therapy is not recommended in severe renal impairment (RI). This study examined RI prevalence among OP women. Nearly a quarter of women had moderate RI, and 3.59% would not be recommended for bisphosphonates, demonstrating a need for better therapeutic alternatives. INTRODUCTION: Bisphosphonates are the recommended first-line treatment for postmenopausal women with OP. However, bisphosphonates are cleared through the kidney, and therapy is not recommended in severe RI due to adverse treatment effects observed with intravenous formulations. The objective of this study was to examine the prevalence of RI among women with OP aged ≥50 years in the USA. METHODS: Women with OP aged ≥50 years were identified using the 2005-2008 National Health and Nutrition Examination Survey (NHANES) data. OP was defined as prior OP diagnosis, previous hip or spine fracture, or measured lumbar spine/femoral neck bone mineral density (BMD) T-score <-2.5. The 2005 Modification of Diet in Renal Disease (MDRD) formula was used to calculate the glomerular filtration rate (GFR). Moderate and severe RI was defined as GFR 30-59 and 15-29 mL/min, respectively. Bisphosphonate therapy was considered not recommended among women with OP if GFR was <35 mL/min. RESULTS: The prevalence of OP among women in USA aged ≥50 years was 27% (12.7 million). Nearly a quarter of women with OP (23.54 ± 2.02%; 2.9 million) had moderate RI and 1.88 ± 0.28% (230,000) had severe RI. Correspondingly, bisphosphonate therapy would not be recommended for an estimated 439,000 women with OP (3.59 ± 0.73%). CONCLUSIONS: Nearly a quarter of postmenopausal women with OP have moderate RI, and over 3% would not be recommended for bisphosphonate treatment. These data reveal a need for better therapeutic alternatives that can be used in this patient population.

Long-term fracture rates seen with continued ibandronate treatment: pooled analysis of DIVA and MOBILE long-term extension studies.

UNLABELLED: Ibandronate reduces the risk of vertebral and non-vertebral fractures versus placebo in postmenopausal women with osteoporosis. This analysis, in which fractures were reported as safety events, showed that long-term use of ibandronate was associated with low fracture rates over 5 years of treatment. INTRODUCTION: A previous post-hoc meta-analysis of 2-3 year studies found that ibandronate regimens with annual cumulative exposure (ACE) of ≥10.8 mg reduced the risk of vertebral and nonvertebral fractures (NVFs) versus placebo in postmenopausal women. This post-hoc analysis used individual patient data from the 2-year monthly oral ibandronate in ladies (MOBILE) and dosing intravenous administration (DIVA) studies, including the 3-year long-term extensions (LTEs), to assess fracture risk in patients treated with ibandronate for 5 years. METHODS: Patients treated for 2 years in MOBILE with monthly oral ibandronate 150 mg (n = 176) and in DIVA with IV ibandronate every 2 months 2 mg (n = 253) or quarterly 3 mg (n = 263) who continued on the same regimens for 3 additional years in the LTEs were included. Three-year placebo data (n = 1,924) were obtained from the ibandronate osteoporosis vertebral fracture trial in North America and Europe (BONE) and IV Fracture Prevention trials. The primary endpoint was clinical fracture rate; clinical fracture data were collected as adverse events. Time to fracture was analyzed using Kaplan-Meier and statistical analysis was conducted using the log-rank test. All clinical fractures included all NVFs and symptomatic vertebral fractures. RESULTS: For ibandronate regimens with ACE ≥10.8 mg, time to fracture was significantly longer for all clinical fractures, NVFs, and clinical vertebral fractures versus placebo (P = 0.005). For all fracture types, the rate of fracture appeared stable during the 5-year treatment period. CONCLUSION: In women with postmenopausal osteoporosis, continuous treatment with ibandronate over 5 years results in low sustained clinical fracture rate.

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial.

UNLABELLED: In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study. INTRODUCTION: The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study. METHODS: In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab. RESULTS: Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine (N = 88) and total hip (N = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort. CONCLUSION: Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated.

Fracture risk assessment in patients with chronic kidney disease.

Fractures are common in patients with chronic kidney disease (CKD) and associated with substantially high morbidity and mortality. Bone mass measurements are commonly used to assess fracture risk in the general population, but the utility of these measurements in patients with CKD, and specifically among those on hemodialysis, is unclear. This review will outline the epidemiology and etiology of fractures in patients with CKD with a particular emphasis on men and women on hemodialysis. As well, we will summarize the published data, which describes the association between risk factors for fracture (including bone mass measurements, biochemical markers of mineral metabolism, and muscle strength) and fractures in patients with CKD. Patients with CKD suffer from fractures due to impairments in bone quantity, bone quality, and abnormalities of neuromuscular function. There is a paucity of evidence on the associations between bone quality, bone turnover markers, neuromuscular function, and fractures in patients with CKD. Furthermore, the complex etiology of fractures combined with the technical limitations of bone mineral density testing, both by dual energy X-ray absorptiometry (DXA) and by peripheral quantitative tomography (pQCT), limits the clinical utility of bone mass measurements for fracture prediction in CKD; this is particularly true among patients with stages 4 and 5 CKD. Further prospective studies to identify noninvasive measures of bone strength that can be used for fracture risk assessment are needed.

Rib fracture as a predictor of future fractures in young and older postmenopausal women: National Osteoporosis Risk Assessment (NORA).

UNLABELLED: A rib fracture history after age 45 was associated with a 5.4-fold increase in new rib fracture risk and a 2.4-fold increase in risk of any new clinical fracture in 155,031 postmenopausal women. A rib fracture history suggests osteoporosis and should be considered when evaluating patients for interventions to prevent fractures. INTRODUCTION: Until recently, little attention was paid to rib fracture as an osteoporosis marker. Emerging evidence suggests rib fracture may be an osteoporotic fracture in men and women. We report the 5-year independent association between baseline rib fracture histories and self-reported future fractures by age (decade) in the NORA cohort (155,031 postmenopausal women, 50-99 years). METHODS: Participants reported fracture history and responded to follow-up surveys at years 1, 3, or 6. Women with a baseline rib fracture history without other fractures were compared with women with no fracture. RESULTS: At baseline, 4,758 (3.07%) women reported a rib fracture history without other fractures; 6,300 women reported 6,830 new clinical fractures, including wrist (2,271), rib (1,891), spine (1,136), hip (941), and forearm (591). Adjusted relative risk (ARR) values (95% confidence interval [CI]) for future fractures in women with rib fracture history versus women with no fracture history were 5.4 (4.8-6.1) at the rib, 2.1 (1.7-2.6) at the spine, and 1.4 (1.1-1.7) at the wrist, and not significant for forearm or hip fractures. Future fracture risk was at least doubled in women with a rib fracture history in all ages: ARR (95% CI) 3.4 (2.8-4.0) for ages 50-59, 2.5 (2.1-3.0) for ages 60-69, 2.0 (1.7-2.3) for ages 70-79, and 2.0 (1.6-2.6) for ages >80. CONCLUSIONS: Rib fracture, the second most common clinical fracture in women (after wrist fracture), predicted future fractures of the rib, wrist, and spine at all ages. Women presenting with rib fractures should be evaluated for appropriate management to prevent future fractures.

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet.

UNLABELLED: Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy. INTRODUCTION: We report the results of a randomized, controlled, clinical study assessing the efficacy and safety of a delayed-release (DR) 35 mg weekly oral formulation of risedronate that allows patients to take their weekly risedronate dose before or immediately after breakfast. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg immediate-release (IR) daily (n = 307) at least 30 min before breakfast, or risedronate 35 mg DR weekly, either at least 30 min before breakfast (BB, n = 308) or immediately following breakfast (FB, n = 307). Bone mineral density (BMD), bone turnover markers (BTMs), fractures, and adverse events were evaluated. The primary efficacy variable was percent change from baseline in lumbar spine BMD at Endpoint. RESULTS: Two hundred fifty-seven subjects (83.7%) in the IR daily group, 252 subjects (82.1%) in the DR FB weekly group, and 258 subjects (83.8%) in the DR BB weekly group completed 1 year. Both DR weekly groups were determined to be non-inferior to the IR daily regimen. Mean percent changes in hip BMD were similar across groups. The magnitude of BTM response was similar across groups; some statistical differences were seen that were small and deemed by investigators to have no major clinical importance. The incidence of adverse events leading to withdrawal and serious adverse events were similar across treatment groups. All three regimens were well tolerated. CONCLUSIONS: Risedronate 35 mg DR weekly is similar in efficacy and safety to risedronate 5 mg IR daily, and will allow patients to take their weekly risedronate dose immediately after breakfast.

Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study.

UNLABELLED: The long-term efficacy and safety of once-monthly ibandronate were studied in this extension to the 2-year Monthly Oral Ibandronate in Ladies (MOBILE) trial. Over 5 years, lumbar spine bone mineral density (BMD) increased from baseline with monthly ibandronate 150 mg (8.4%). Long-term monthly ibandronate is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis. INTRODUCTION: Once-monthly therapy with ibandronate has been studied for up to 5 years in a long-term extension (LTE) to the 2 year MOBILE trial. METHODS: This multicenter, double-blind extension study of monthly ibandronate involved postmenopausal women who had completed 2 years of the MOBILE core study, with ≥75% adherence. Patients were reallocated, or were randomized from daily therapy, to ibandronate 100 mg monthly or 150 mg monthly for a further 3 years. RESULTS: A pooled intent-to-treat (ITT) analysis of 344 patients receiving monthly ibandronate from the core MOBILE baseline showed increases over 5 years in lumbar spine BMD (8.2% with 100 mg and 8.4% with 150 mg). Three-year data relative to MOBILE LTE baseline in the full ITT population of all 698 patients randomized or reallocated from MOBILE (including those previously on daily treatment) showed, on average, maintenance of proximal femur BMD gains achieved in the core 2-year study, with further small gains in lumbar spine BMD. In general, maintenance of efficacy was also indicated by markers of bone metabolism. CONCLUSIONS: There were no tolerability concerns or new safety signals. Monthly treatment with ibandronate 100 and 150 mg is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis.

What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?

Pharmacologic osteoporosis therapy, particularly anti-resorptives, is recommended in postmenopausal women with clinical risk factors for fracture. Treatment decisions should be made based on the relative benefit-risk profile in different patient populations. Emerging options [e.g., selective estrogen receptor modulators (SERMs) and denosumab] may hold promise for providing protection from bone loss and for fracture risk reduction.Osteoporosis, the most common clinical disorder of bone metabolism, is characterized by low bone mineral density, deterioration of microarchitecture, and a consequent increase in bone fragility and risk of fracture. Pharmacologic therapy is recommended in postmenopausal women with clinical risk factors for fracture and includes anti-resorptive agents such as bisphosphonates, hormone therapy, SERMs, and calcitonin. The anabolic agent teriparatide (parathyroid hormone) is usually reserved for high-risk patients or those with glucocorticoid-induced osteoporosis. Strontium ranelate, available outside the USA, has both anti-resorptive and anabolic properties. Supplementation with calcium and vitamin D is recommended for all women aged 50 years and older. Bisphosphonates are often considered first-line therapy for osteoporosis and have the largest base of clinical trial data showing efficacy for global fracture risk reduction. Low-dose hormone therapy is appropriate for younger women who are experiencing other menopausal symptoms. In women for whom bisphosphonates are not appropriate or not tolerated or in younger postmenopausal women who have a low risk for hip fracture, SERMs are a suitable treatment option. Calcitonin is designated for patients who are unable or unwilling to tolerate other osteoporosis agents. Emerging options, including newer SERMs (e.g., bazedoxifene and lasofoxifene) and the monoclonal antibody denosumab, may hold promise for providing protection from bone loss and for fracture risk reduction. Because no single agent is appropriate for all patients, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.

"Evidence-based" or "logic-based" medicine?

Low trauma fractures are the cardinal manifestation of osteoporosis. Their occurrence supersedes bone mineral density in deciding whether specific therapy is warranted. We therefore disagree with the notion that a densitometric threshold for treatment should be applied to patients over age 50 who suffer low trauma distal radius fracture.

Long-term Case Reports Demonstrating Use of Porcine Collagen Matrix to Augment Width and Thickness of Keratinized Gingiva.

Gingival augmentation therapy is intended to create a healthy band of attached keratinized tissue to inhibit further gingival recession, facilitate plaque control, and improve patient comfort. Although an effective treatment for gingival augmentation procedures, the often-used autogenous epithelialized palatal graft has several drawbacks, including the need for a second surgical site to harvest the graft, the risk of such complications as damage to neurovascular tissue and poor healing of the donor site, and potential color and texture discrepancies of the grafted site. The use of a resorbable xenogeneic collagen-based matrix may be considered as a treatment alternative to augment soft tissue. The authors describe the application of such a graft that is made from purified porcine type I and type III collagen and processed without the addition of chemical cross-linkers. Two cases are presented that demonstrate the clinical advantages of this material compared to autogenous palatal grafts when augmenting the width and thickness of attached keratinized gingiva.