Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

CONTEXT: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. OBJECTIVE: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. METHODS: A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. RESULTS: Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). CONCLUSION: It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

OBJECTIVE: Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). METHODS: Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. RESULTS: Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. CONCLUSIONS: The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Extensive expertise in endocrinology: advances in the management of glucocorticoid-induced osteoporosis.

Osteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling. Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency, or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first-line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first-line option in very high-risk individuals.

The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.

This systematic review (SR) assessed the use of denosumab (Prolia®) to treat osteoporosis in cancer patients receiving endocrine therapy. Denosumab was found to prevent vertebral fractures and improve bone mineral density in cancer patients with osteoporosis. This is the first SR to assess treating osteoporotic cancer patients with denosumab. PURPOSE: This study assessed the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs) (bazedoxifene, raloxifene) and placebo for the treatment of osteoporosis in hormone-sensitive cancer patients receiving endocrine therapy (men with prostate cancer [MPC] on hormone ablation therapy [HAT], and women with breast cancer [WBC] on adjuvant aromatase inhibitor therapy [AAIT]). METHODS: Systematic literature searches were conducted in three biomedical databases to identify randomized controlled trials (RCTs). Frequentist network meta-analyses and/or pairwise meta-analyses were performed on predetermined outcomes (i.e., vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, treatment-related adverse events [AEs], serious AEs [SAEs], withdrawal due to treatment-related AEs). RESULTS: A total of 14 RCTs (15 publications) were included. Denosumab was found to prevent vertebral fractures in cancer patients receiving endocrine therapy, relative to placebo. Similarly, denosumab, zoledronate, and alendronate improved BMD at the femoral neck (FN) and lumbar spine (LS) in MPC on HAT, relative to placebo. Denosumab, ibandronate and risedronate improved BMD at the LS and total hip (TH) in WBC on AAIT, relative to placebo. Denosumab and risedronate improved trochanteric (TRO) BMD in WBC on AAIT, relative to placebo. Similarly, denosumab improved FN BMD in WBC on AAIT. CONCLUSION: In MPC on HAT, denosumab (relative to placebo) was effective at preventing vertebral fractures and improving BMD at the FN and LS. Moreover, in WBC on AAIT, denosumab (relative to placebo) improved BMD at the FN, LS, TH, and TRO, as well as prevent vertebral fracture.

[A randomized double-blinded placebo-controlled clinical trial of minodronate tablet in postmenopausal Chinese women with osteoporosis].

Objective: To verify the efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis. Methods: In this randomized, double-blinded, placebo-controlled trial, 262 postmenopausal women were enrolled. Patients were randomized to receive daily oral minodronate 1 mg with supplements of 500 mg calcium and 200 U vitamin D3 (n=130) or placebo (n=132) with daily supplements of 500 mg calcium and 200 U vitamin D3, for 48 weeks. The primary endpoint was the average bone mineral density (BMD) change in the lumbar vertebrae 48 weeks post-treatment. Secondary outcome measures was the incidence of vertebral fractures. Safety assessments included the rate of adverse events. Results: At the end of 48 weeks treatment, the average BMD change rate from baseline were: full analysis set results: (3.52±4.82)% in the minodronate group and (2.00±5.74)% in the placebo group; per-protocol set results: (3.99±5.05)% in the minodronate group and (2.07±6.20)% in the placebo group; the differences were all significant (all P<0.05). Vertebral fracture occured in 3 patients (2.3%, 3/132) in the placebo group, and 1 case (0.8%, 1/130) in the minodronate group (P>0.05). The incidence of adverse events was 71.5% (93/130) in the minodronate group and 78.0% (103/132) in the placebo group (P>0.05). Conclusion: Minodronate is effective and safe in the treatment of postmenopausal osteoporosis without severe side effects.

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis.

AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor-α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures. METHODS: Patients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2-year follow-up BMD measurements were included. BMD of lumbar spine (L1-L4) and hip (total proximal femur) were measured using dual-energy X-ray absorptiometry. Spinal radiographs (Th4-L4) were scored for vertebral fractures according to the Genant method. RESULTS: In the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z-scores increased significantly; median from -1.5 (interquartile range [IQR] -2.2 to 0.4) to 0.1 (IQR -1.5 to 1.0); P < .001 and median from -1.0 (IQR -1.6 to -0.7) to -0.8 (IQR -1.2 to 0.0); P = .006 over 2 years, respectively. In patients also treated with tumour necrosis factor-α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2-year change +8.6% [IQR 2.4 to 19.6; P = .009] and +3.6% [IQR 0.7-9.0; P = .007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2-year change +3.6%; IQR 0.7 to 9.0; P = .011) and no improvement was seen in hip BMD (median -0.6%; IQR -3.1 to 5.1; P = .61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle-aged men. CONCLUSION: This explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred.

An easy way to determine bone mineral density and predict pelvic insufficiency fractures in patients treated with radiotherapy for cervical cancer.

PURPOSE: The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer. METHODS: 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm3), V50Gy, Dmean, and Dmax. RESULTS: Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p < 0.05). The BMD of the contoured PIF, however, when comparing to the mPIF, did not reach significance (p < 0.49). The difference of the V50Gy of the sacrum in the PIF group compared to the other (OTH) patients, i.e. those without PIF, did not reach significance. CONCLUSION: The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Bone Metabolism Impairment in Heart Transplant: Results From a Prospective Cohort Study.

BACKGROUND: Data on the prevention of fractures after heart transplant (HTx) are controversial in the literature. Understanding the effects of HTx on bone may guide appropriate treatments in this high-risk population. METHODS: Seventy adult HTx patients were followed for 12 months. Clinical and laboratory parameters, bone mineral density, microarchitecture, and vertebral fractures were assessed at baseline (after intensive care unit discharge) and at 6 and 12 months. Patients received recommendations regarding calcium intake and vitamin D supplementation after HTx. RESULTS: At baseline, 27% of patients had osteoporosis, associated with the length of hospitalization before HTx (P = 0.001). Bone mineral density decreased in the first 6 months, with partial recovery later. Bone microarchitecture deteriorated, mainly in the trabecular bone in the first 6 months and cortical bone in the subsequent 6 months. At baseline, 92.9% of patients had vitamin D levels <30 ng/mL and 20.0% <10 ng/mL. Patients also had calcium at the lower limit of normal, high alkaline phosphatase, and high bone resorption biomarker. These abnormalities were suggestive of impaired bone mineralization and normalized at 6 months with correction of vitamin D deficiency. The majority of vertebral fractures were identified at baseline (23% of patients). After multivariate analyses, only a lower fat mass persisted as a risk factor for vertebral fractures (odds ratio, 1.23; 95% confidence interval, 1.04-1.47; P = 0.012). CONCLUSIONS: High frequencies of densitometric osteoporosis, vitamin D deficiency, bone markers abnormalities, and vertebral fractures were observed shortly after HTx. Calcium and vitamin D supplementation should be the first step in correcting bone mineralization impairment before specific osteoporosis treatment.

Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials.

Vitamin K may affect bone mineral density and fracture incidence. Since publication of a previous systematic review the integrity of some of the previous evidence has been questioned and further trials have been published. Therefore an update to the systematic review was required. INTRODUCTION: This systematic review was designed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density and reducing fractures in adults. METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, clinicaltrials.gov, and WHO-ICTRP were searched for eligible trials. Randomised controlled trials assessing oral vitamin K supplementation that assessed bone mineral density or fractures in adult populations were included. A total of 36 studies were identified. Two independent reviewers extracted data using a piloted extraction form. RESULTS: For post-menopausal or osteoporotic patients, meta-analysis showed that the odds of any clinical fracture were lower for vitamin K compared to controls (OR, 0.72, 95%CI 0.55 to 0.95). Restricting the analysis to low risk of bias trials reduced the OR to 0.76 (95%CI, 0.58 to 1.01). There was no difference in vertebral fractures between the groups (OR 0.96, 95%CI 0.83 to 1.11). In the bone mineral density meta-analysis, percentage change from baseline at the lumbar spine was higher at 1 year (MD 0.93, 95%, CI - 0.02 to 1.89) and 2 years (MD 1.63%, 95%CI 0.10 to 3.16) for vitamin K compared to controls; however, removing trials at high risk of bias tended to result in smaller differences that were not statistically significant. At 6 months, it was higher in the hip (MD 0.42%, 95%CI 0.01 to 0.83) and femur (MD 0.29%, 95%CI 0.17 to 0.42). There was no significant difference at other anatomical sites. CONCLUSIONS: For post-menopausal or osteoporotic patients, there is no evidence that vitamin K affects bone mineral density or vertebral fractures; it may reduce clinical fractures; however, the evidence is insufficient to confirm this. There are too few trials to draw conclusions for other patient groups.

Rates of osteoporosis screening and treatment following vertebral fracture.

BACKGROUND CONTEXT: Osteoporosis remains an underrecognized and undertreated disease entity in the orthopaedic setting, accounting for substantial long-term morbidity and mortality. Osteoporosis is often not diagnosed or treated until multiple fractures have occurred. Vertebral compression fractures are the most common sentinel fracture, providing an opportunity to intervene with antiresorptive therapy before more debilitating fractures occur. Little data has been published on osteoporosis screening and treatment following vertebral fractures. Further elucidation of the osteoporosis care gap in these patients is warranted. PURPOSE: To demonstrate the current state of post vertebral fracture osteoporosis management at a large tertiary care center with no established secondary fracture prevention program. STUDY DESIGN: Retrospective cohort study. SETTING: A large tertiary care hospital or one of its affiliated community hospitals. PATIENT SAMPLE: All 2,933 patients, 50 years of age or older, who presented to an emergency department with a new vertebral fracture between 2008 and 2014. OUTCOME MEASURES: The physiological measures are rates of new fractures within 2 years following first vertebral fracture. PATIENT CARE METRICS: Post vertebral fracture rates of dual energy X-ray absorptiometry (DXA) testing, calcium and vitamin D supplementation, and pharmacotherapy for osteoporosis within 1 year postfracture, and more than 1 year postfracture. Linear trend of the rate of new antiosteoporosis pharmacotherapy among previously antiosteoporosis medication naive patients within 1 year of fracture over time from 2008 to 2014. METHODS: All patients aged 50 years or older presenting to an emergency department with a vertebral fracture between 2008 and 2014 were included. Only an individual's first documented vertebral fracture was considered. Individuals were assessed for DXA screening, calcium and vitamin D supplementation, treatment with an antiosteoporosis medication, and additional fractures following incident vertebral fracture. Statistical analyses included descriptive statistics and a simple logistic regression. No specific funding was provided for this study. The authors of this study report no relevant financial conflicts of interests or associated biases. RESULTS: Between 2008 and 2014, 2,933 unique patients were seen at an included emergency department for one or more vertebral fracture encounters. Ninety-eight percent did not receive a DXA scan within the preceding 2 years or 1 year following fracture. Seven percent of patients were started on antiresorptive therapy after their fracture, with 341 (5%) starting within 1 year of fracture and 211 (2%) starting thereafter. Twenty-one percent (n=616) had taken an antiresorptive medication before their fracture. Seventy three percent (n=2,128) were never prescribed antiresorptive therapy. Treatment rates slightly decreased over time. Thirty eight percent of patients presenting with a vertebral fracture (n=1,115) went on to develop a second fragility fracture within 2 years. CONCLUSIONS: In the absence of a specific local program to improve secondary fracture prevention following minimal trauma spinal fractures, recognition and treatment of osteoporosis in patients at this institution remained dismal over time despite numerous calls to action on the topic in the orthopaedic literature and elsewhere. Undertreatment of osteoporosis puts patients at increased risk of incurring additional fractures. Within 2 years, 38% of the patients in this sample developed an additional fragility fracture. This study demonstrates a profound post vertebral fracture osteoporosis care gap.

Visualisation of the unmet treatment need of osteoporotic fracture in Taiwan: A nationwide cohort study.

AIMS: Recent clinical guidelines have suggested that patients experience an osteoporotic fracture should initiate anti-osteoporosis medications (AOMs). However, whether clinical guidelines translate well in "real-world" practices remain questioned. This study aimed to evaluate the "real-world" prescription pattern of AOMs and visualise the unmet treatment needs in different geographical areas in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The treatment rate was defined as the proportion of patients receiving AOMs within 1 year after their index fracture. The qualitative geographical information systems approach was adopted to visualise the treatment needs of postfracture patients in different geographical areas. RESULTS: Our study included 276,492 patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The proportion of patients who received AOMs within 1 year after their index fracture increased with age and differed with fracture types and sex. For patients with hip fractures, the treatment rate ranged from 3.43% to 20.88% for female patients and from 0.69% to 10.04% for male patients in different age groups. For patients with vertebral fractures, the treatment rate ranged from 3.23% to 37.08% for female patients and from 1.85% to 23.05% for male patients. Cities in the mid-northern and southern areas of Taiwan had the highest unmet treatment need, with a treatment rate of less than 15%. CONCLUSION: The treatment rate of osteoporotic fractures with AOMs was diverse and suboptimal in Taiwan, especially among male patients. This study used a visualisation technique to display information about the treatment status in different geographical areas and help policymakers allocate resource appropriately.

Establishing a hospital based fracture liaison service to prevent secondary insufficiency fractures.

In the aging population worldwide, osteoporosis is a relatively common condition and a major cause of long-term morbidity. Initial fragility fractures can lead to subsequent fractures. After a vertebral fracture, the risk of any another fracture increases 200% and that of a subsequent hip fracture increases 300%. For starting a hospital based Fracture Liaison Service (FLS) program, the nucleus is based on a physician champion, a FLS coordinator, and a nurse manager. A Fracture Liaison Service (FLS) is a multidisciplinary system approach to reducing subsequent fracture risk in patients with a recent fragility fracture due to compromised bone health by identifying them at or close to the time when they are treated at the hospital for fracture and providing them with easy access to osteoporosis care. It has been shown that when compared to other models such as referral letters to primary care physicians or endocrinologists, the FLS model results in a higher rate of diagnosis and treatment with less attrition in the posffracture phase. Insufficiency fracture care requires more than surgery to stabilize a fractured bone. The FLS program provides an opportunity to treat osteoporosis from a public health perspective rather than leaving this to the whims of individual physicians. This is achieved by providing a seamless integration of care by health care providers, nursing staff and administration. The FLS can be adapted to any model of care including academic health systems. FLS provides a holistic approach to identify patients as well as to provide evidence-based interventions to prevent subsequent fractures. The long term goal is that internationally FLS will result in in decreased fracture-related morbidity, mortality and overall health care expenditure.

Pharmacological treatment of osteoporosis in the oldest old.

The incidence of osteoporotic fractures increases with age. Consequently, the global prevalence of osteoporotic fractures will increase with the aging of the population. In old age, osteoporosis is associated with a substantial burden in terms of morbidity and mortality. Nevertheless, osteoporosis in old age continues to be underdiagnosed and undertreated. This may, at least partly, be explained by the fact that evidence of the antifracture efficacy of osteoporosis treatments comes mainly from randomized controlled trials in postmenopausal women with a mean age of 70-75 years. However, in the last years, subgroup analyses of these landmark trials have been published investigating the efficacy and safety of osteoporosis treatment in the very elderly. Based on this evidence, this narrative review discusses the pharmacological management of osteoporosis in the oldest old (≥80 years). Because of the high prevalence of calcium and/or vitamin D deficiency in old age, these supplements are essential in the management of osteoporosis in the elderly people. Adding antiresorptive or anabolic treatments or combinations, thereof, reduces the risk of vertebral fractures even more, at least in the elderly with documented osteoporosis. The reduction of hip fracture risk by antiresorptive treatments is less convincing, which may be explained by insufficient statistical power in some subanalyses and/or a higher impact of nonskeletal risk factors in the occurrence of hip fractures. Compared with younger individuals, a larger absolute risk reduction is observed in the elderly because of the higher baseline fracture risk. Therefore, the elderly will benefit more of treatment. In addition, current osteoporosis therapies also appear to be safe in the elderly. Although more research is required to further clarify the effect of osteoporosis drugs in the elderly, especially with respect to hip fractures, there is currently sufficient evidence to initiate appropriate treatment in the elderly with osteoporosis and osteoporotic fractures.

Interventions to prevent and treat corticosteroid-induced osteoporosis and prevent osteoporotic fractures in Duchenne muscular dystrophy.

BACKGROUND: Corticosteroid treatment is considered the 'gold standard' for Duchenne muscular dystrophy (DMD); however, it is also known to induce osteoporosis and thus increase the risk of vertebral fragility fractures. Good practice in the care of those with DMD requires prevention of these adverse effects. Treatments to increase bone mineral density include bisphosphonates and vitamin D and calcium supplements, and in adolescents with pubertal delay, testosterone. Bone health management is an important part of lifelong care for patients with DMD. OBJECTIVES: To assess the effects of interventions to prevent or treat osteoporosis in children and adults with DMD taking long-term corticosteroids; to assess the effects of these interventions on the frequency of vertebral fragility fractures and long-bone fractures, and on quality of life; and to assess adverse events. SEARCH METHODS: On 12 September 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus to identify potentially eligible trials. We also searched the Web of Science ISI Proceedings (2001 to September 2016) and three clinical trials registries to identify unpublished studies and ongoing trials. We contacted correspondence authors of the included studies in the review to obtain information on unpublished studies or work in progress. SELECTION CRITERIA: We considered for inclusion in the review randomised controlled trials (RCTs) and quasi-RCTs involving any bone health intervention for corticosteroid-induced osteoporosis and fragility fractures in children, adolescents, and adults with a confirmed diagnosis of DMD. The interventions might have included oral and intravenous bisphosphonates, vitamin D supplements, calcium supplements, dietary calcium, testosterone, and weight-bearing activity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed reports and selected potential studies for inclusion, following standard Cochrane methodology. We contacted study authors to obtain further information for clarification on published work, unpublished studies, and work in progress. MAIN RESULTS: We identified 18 potential studies, of which two, currently reported only as abstracts, met the inclusion criteria for this review. Too little information was available for us to present full results or adequately assess risk of bias. The participants were children aged five to 15 years with DMD, ambulant and non-ambulant. The interventions were risedronate versus no treatment in one trial (13 participants) and whole-body vibration versus a placebo device in the second (21 participants). Both studies reported improved bone mineral density with the active treatments, with no improvement in the control groups, but the abstracts did not compare treatment and control conditions. All children tolerated whole-body vibration treatment. No study provided information on adverse events. Two studies are ongoing: one investigating whole-body vibration, the other investigating zoledronic acid. AUTHORS' CONCLUSIONS: We know of no high-quality evidence from RCTs to guide use of treatments to prevent or treat corticosteroid-induced osteoporosis and reduce the risk of fragility fractures in children and adults with DMD; only limited results from two trials reported in abstracts were available. We await formal trial reports. Findings from two ongoing relevant studies and two trials, for which only abstracts are available, will be important in future updates of this review.

Relationship between baseline characteristics and response to risedronate treatment for osteoporosis: data from three Japanese phase III trials.

We evaluated the influence of baseline age, bone mineral density (BMD), and serum levels of vitamin D on the response to risedronate treatment. Risedronate consistently increased BMD, but our results suggest vitamin D supplementation may be necessary to achieve optimal treatment effect. Furthermore, early intervention may help prevent bone fractures. INTRODUCTION: We aimed to investigate the influence of baseline age, BMD, and vitamin D insufficiency on the response to risedronate treatment. METHODS: Data regarding 1447 patients was obtained from the registries of three phase III clinical trials of risedronate. The response to treatment was expressed in terms of BMD increase and occurrence of new vertebral fractures. The patients were stratified by baseline values for age (<65, 65-72, and ≥72 years), lumbar spine BMD T-score (osteoporotic, <-2.5; and non-osteoporotic, ≥- 2.5), and serum levels of 25-hydroxyvitamin D (deficient, <21 ng/mL; and non-deficient, ≥21 ng/mL). RESULTS: Risedronate consistently increased lumbar spine BMD in all the groups, with similar percentage and absolute increments in all the age tertiles. The percentage, but not absolute, increment in BMD was significantly higher (p = 0.0003) in the osteoporotic than that in the non-osteoporotic patients (baseline). Of the 1330 patients whose baseline serum levels of 25-hydroxyvitamin D were available, 44.7% had vitamin D deficiency (<20 ng/mL), while 89.2% had insufficiency (<30 ng/mL). The percentage and absolute increments in BMD were lower (p < 0.05 and p < 0.01, respectively) in the vitamin D-deficient than those in the non-deficient patients. New vertebral fractures occurred in 1.5 and 0.8% of the osteoporotic and non-osteoporotic patients, respectively (end of the treatment). CONCLUSIONS: Therapeutic response in elderly patients is consistent, but early initiation of risedronate treatment may help prevent fractures. Risedronate-induced increase in BMD is lower in patients with vitamin D deficiency, suggesting that vitamin D supplementation is important to achieve optimal treatment response.

Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment.

Effective secondary fracture prevention: implementation of a global benchmarking of clinical quality using the IOF Capture the Fracture® Best Practice Framework tool.

UNLABELLED: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. INTRODUCTION: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation's Capture the Fracture® programme developed a Best Practice Framework (BPF) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. METHODS: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black (insufficient) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service (FLS) map. RESULTS: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. CONCLUSION: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.

Management of osteoporosis in rheumatoid arthritis patients.

INTRODUCTION: In rheumatoid arthritis (RA) patients, the risk of both vertebral and non-vertebral fractures is roughly doubled, which is for an important part caused by inflammation-mediated amplification of bone loss and by immobilization. New treatments have become available in the last two decades to treat both RA and osteoporosis. AREAS COVERED: Epidemiology and assessment of osteoporosis and fracture risk (including the influence of RA disease activity and bone-influencing medications such as glucocorticoids), the importance of vertebral fracture assessment in addition to bone density measurement in patients with RA, the use of disease-modifying antirheumatic drugs and their effects on generalized bone loss, and current and possible future anti-osteoporotic pharmacotherapeutic options are discussed with special focus on RA. EXPERT OPINION: Assessment of osteoporosis in RA patients should include evaluation of the effects of disease activity and bone-influencing medications such as (the dose of) glucocorticoids, above standard risk factors for fractures or osteoporosis as defined by the FRAX instrument. Disease-modifying antirheumatic drugs are now well able to control disease activity using treat to target strategies. This lowering of disease activity by antirheumatic medications such as anti-TNF-α results in hampering of generalized bone loss; however, no fracture data are currently available. When treating osteoporosis in RA patients, additional focus should be on calcium supplementation, particularly in glucocorticoid users, and also on sufficient vitamin D use. Several anti-osteoporotic medications are now on the market; oral bisphosphonates are most commonly used, but in recent years, more agents have entered the market such as the parenteral antiresorptives denosumab (twice yearly) and zoledronic acid (once yearly), and the anabolic agent parathyroid hormone analogues. New agents, such as odanacatib and monoclonal antibodies against sclerostin, are now being tested and will most likely enlarge the possibilities of osteoporosis treatment in RA patients.

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT).

SUMMARY: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. INTRODUCTION: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. METHODS: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. RESULTS: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. CONCLUSIONS: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.

Efficacy, effectiveness and side effects of medications used to prevent fractures.

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long-term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit-risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and 'drug holidays' should be considered at this time. Further studies are needed to guide clinical practice in this area.