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Osteoporosis: HELP
Articles by Andrew B. Grey
Based on 50 articles published since 2008

Between 2008 and 2019, A. Grey wrote the following 50 articles about Osteoporosis.
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Osteoporosis and Fracture Risk in Men with Prostate Cancer. 2016

Grey, Andrew. ·Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: a.grey@auckland.ac.nz. ·Eur Urol · Pubmed #26749094.

ABSTRACT: -- No abstract --

2 Editorial Vitamin D: a place in the sun? 2010

Grey, Andrew / Bolland, Mark. · ·Arch Intern Med · Pubmed #20625012.

ABSTRACT: -- No abstract --

3 Review Should we prescribe calcium or vitamin D supplements to treat or prevent osteoporosis? 2015

Bolland, M J / Grey, A / Reid, I R. ·a Department of Medicine , University of Auckland , Auckland , New Zealand. ·Climacteric · Pubmed #26473773.

ABSTRACT: Systematic reviews of randomized, controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. Meta-analyses of large RCTs of calcium and/or vitamin D supplements completed in the last 15 years provide strong evidence for clinical recommendations. These meta-analyses with data for > 50,000 older adults reported that calcium with or without vitamin D has only weak, inconsistent effects on fracture, and that vitamin D without calcium has no effect on fracture. Only one RCT of co-administered calcium and vitamin D in frail, institutionalized, elderly women with low dietary calcium intake and vitamin D levels showed significant reductions in fracture risk. These RCTs have also reported previously unrecognized adverse events of calcium supplements including kidney stones, myocardial infarction, hypercalcemia, and hospitalization with acute gastrointestinal symptoms. The small risk of these important adverse effects, together with the moderate risk of minor side-effects such as constipation, probably outweighs any benefits of calcium supplements on fracture. These data suggest the role for calcium and vitamin D supplements in osteoporosis management is very limited. Neither calcium nor vitamin D supplements should be recommended for fracture prevention in community-dwelling adults, although vitamin D should be considered for prevention of osteomalacia in at-risk individuals.

4 Review Adverse skeletal effects of drugs - beyond Glucocorticoids. 2015

O'Sullivan, Susannah / Grey, Andrew. ·Department of Pharmacology, University of Auckland, Auckland, New Zealand. ·Clin Endocrinol (Oxf) · Pubmed #25039381.

ABSTRACT: Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management.

5 Review Results of observational studies: analysis of findings from the Nurses' Health Study. 2014

Tai, Vicky / Grey, Andrew / Bolland, Mark J. ·Department of Medicine, University of Auckland, Auckland, New Zealand. ·PLoS One · Pubmed #25330007.

ABSTRACT: BACKGROUND: The role of observational studies in informing clinical practice is debated, and high profile examples of discrepancies between the results of observational studies and randomised controlled trials (RCTs) have intensified that debate. We systematically reviewed findings from the Nurses' Health Study (NHS), one of the longest and largest observational studies, to assess the number and strength of the associations reported and to determine if they have been confirmed in RCTs. METHODS: We reviewed NHS publication abstracts from 1978-2012, extracted information on associations tested, and graded the strength of the reported effect sizes. We searched PubMed for RCTs or systematic reviews for 3 health outcomes commonly reported in NHS publications: breast cancer, ischaemic heart disease (IHD) and osteoporosis. NHS results were compared with RCT results and deemed concordant when the difference in effect sizes between studies was ≤0.15. FINDINGS: 2007 associations between health outcomes and independent variables were reported in 1053 abstracts. 58.0% (1165/2007) were statistically significant, and 22.2% (445/2007) were neutral (no association). Among the statistically significant results that reported a numeric odds ratio (OR) or relative risk (RR), 70.5% (706/1002) reported a weak association (OR/RR 0.5-2.0), 24.5% (246/1002) a moderate association (OR/RR 0.25-0.5 or 2.0-4.0) and 5.0% (50/1002) a strong association (OR/RR ≤0.25 or ≥4.0). 19 associations reported in NHS publications for breast cancer, IHD and osteoporosis have been tested in RCTs, and the concordance between NHS and RCT results was low (≤25%). CONCLUSIONS: NHS publications contain a large number of analyses, the majority of which reported statistically significant but weak associations. Few of these associations have been tested in RCTs, and where they have, the agreement between NHS results and RCTs is poor.

6 Review A comparison of adverse event and fracture efficacy data for strontium ranelate in regulatory documents and the publication record. 2014

Bolland, Mark J / Grey, Andrew. ·Department of Medicine, University of Auckland, Auckland, New Zealand. ·BMJ Open · Pubmed #25293384.

ABSTRACT: OBJECTIVE: Recently, the European Medicines Agency reported that strontium ranelate increases myocardial infarction risk in postmenopausal women, 8.5 years after it was registered for use in osteoporosis. Unreported serious adverse events in clinical trials for other pharmaceuticals have been described in recent years. We assessed reporting of adverse events and fracture efficacy of strontium. METHODS: We compared data on adverse effects (myocardial infarction, venous thromboembolism and pulmonary embolism) and fracture efficacy of strontium in publicly available regulatory documents with data in publications retrieved from searching PubMed. RESULTS: We identified 5 regulatory documents and 9 primary publications of 7 randomised, placebo-controlled trials of strontium that reported relevant data. We identified several areas of concern in these reports: the increased risk of myocardial infarction with strontium was not identified in a pivotal phase 3 clinical trial despite specific regulatory review of cardiovascular events; data on myocardial infarction were not included in any primary publication; increased risks of venous thromboembolism and pulmonary embolism with strontium were not reported in either of the phase 3 clinical trials; data on venous thromboembolism were reported in only 5 of 9 primary publications, data on pulmonary embolism in only 2 of 9 primary publications, and either was discussed in <50% of subsequent review articles. There were differences in participant numbers, fracture cases and venous thromboembolism cases between regulatory documents and primary publications. Based on all available data from primary publications and regulatory documents, the number of fractures prevented by strontium use is similar to the number of extra cases of venous thromboembolism, pulmonary embolism and myocardial infarction caused by strontium use. CONCLUSIONS: The risks of strontium use are similar to the benefits. Full disclosure of the clinical trial data and regulatory documents would allow clinicians and their patients to decide whether use of the drug is worthwhile.

7 Review Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. 2014

Reid, Ian R / Bolland, Mark J / Grey, Andrew. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand. Electronic address: i.reid@auckland.ac.nz. · Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. · Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand. ·Lancet · Pubmed #24119980.

ABSTRACT: BACKGROUND: Findings from recent meta-analyses of vitamin D supplementation without co-administration of calcium have not shown fracture prevention, possibly because of insufficient power or inappropriate doses, or because the intervention was not targeted to deficient populations. Despite these data, almost half of older adults (older than 50 years) continue to use these supplements. Bone mineral density can be used to detect biologically significant effects in much smaller cohorts. We investigated whether vitamin D supplementation affects bone mineral density. METHODS: We searched Web of Science, Embase, and the Cochrane Database, from inception to July 8, 2012, for trials assessing the effects of vitamin D (D3 or D2, but not vitamin D metabolites) on bone mineral density. We included all randomised trials comparing interventions that differed only in vitamin D content, and which included adults (average age >20 years) without other metabolic bone diseases. We pooled data with a random effects meta-analysis with weighted mean differences and 95% CIs reported. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I(2) statistic. The primary endpoint was the percentage change in bone mineral density from baseline. FINDINGS: Of 3930 citations identified by the search strategy, 23 studies (mean duration 23·5 months, comprising 4082 participants, 92% women, average age 59 years) met the inclusion criteria. 19 studies had mainly white populations. Mean baseline serum 25-hydroxyvitamin D concentration was less than 50 nmol/L in eight studies (n=1791). In ten studies (n=2294), individuals were given vitamin D doses less than 800 IU per day. Bone mineral density was measured at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total body, or forearm) in each study, so 70 tests of statistical significance were done across the studies. There were six findings of significant benefit, two of significant detriment, and the rest were non-significant. Only one study showed benefit at more than one site. Results of our meta-analysis showed a small benefit at the femoral neck (weighted mean difference 0·8%, 95% CI 0·2-1·4) with heterogeneity among trials (I(2)=67%, p<0·00027). No effect at any other site was reported, including the total hip. We recorded a bias toward positive results at the femoral neck and total hip. INTERPRETATION: Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate. FUNDING: Health Research Council of New Zealand.

8 Review The effect of treatments for osteoporosis on mortality. 2013

Grey, A / Bolland, M J. ·Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz ·Osteoporos Int · Pubmed #23076683.

ABSTRACT: The incidence of osteoporotic fractures increases exponentially in later life, in parallel with the progression of frailty and the risk of dying. Several pharmacologic therapies are now available that reduce the risk of fragility fractures. Data from observational studies report that osteoporotic fractures are associated with an increased risk of dying, particularly in the first few years after an event, and that, in osteoporotic populations, bisphosphonate therapy is associated with a reduced risk of death. Data emerging from randomised controlled trials suggest that drugs which significantly reduce fracture risk might also prolong survival in osteoporotic populations. Further research into the nature, magnitude and mechanisms of the effects of osteoporosis treatments on mortality is required, but in the interim, clinicians and their patients should consider the available data in their deliberations about the use of these medications.

9 Review Calcium supplementation: balancing the cardiovascular risks. 2011

Reid, Ian R / Bolland, Mark J / Sambrook, Philip N / Grey, Andrew. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz ·Maturitas · Pubmed #21621353.

ABSTRACT: Calcium supplementation has been widely accepted as a key strategy in the prevention and treatment of osteoporosis. Its role has been undermined, to some extent, by its disappointing effects on fracture in randomised controlled trials, but its use has continued to be encouraged on the grounds that it is physiologically appealing, and is unlikely to cause harm. The latter assumption is now under threat from accumulating evidence that calcium supplement use is associated with an increased risk of myocardial infarction and, possibly, stroke. The latest data, based on meta-analysis of trials involving 29,000 participants, indicate that this risk is not mitigated by co-administration of vitamin D, and that the number of cardiovascular events caused is likely to be greater than the number of fractures prevented. These findings indicate that calcium supplementation probably does not have a role as a routine preventative agent and that dietary advice is the appropriate way to attain an adequate calcium intake in most situations. Patients at high risk of fracture need to take interventions of proven anti-fracture efficacy. Available evidence suggests that this efficacy is not dependent on the co-administration of calcium supplements.

10 Review Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. 2011

Bolland, Mark J / Grey, Andrew / Avenell, Alison / Gamble, Greg D / Reid, Ian R. ·Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand. ·BMJ · Pubmed #21505219.

ABSTRACT: OBJECTIVES: To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk. DESIGN: Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies. Data source WHI CaD Study, a seven year, randomised, placebo controlled trial of calcium and vitamin D (1g calcium and 400 IU vitamin D daily) in 36,282 community dwelling postmenopausal women. Main outcome measures Incidence of four cardiovascular events and their combinations (myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke) assessed with patient-level data and trial-level data. RESULTS: In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events. In the 16,718 women (46%) who were not taking personal calcium supplements at randomisation the hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (P = 0.05 for clinical myocardial infarction or stroke, P = 0.04 for clinical myocardial infarction or revascularisation), whereas in the women taking personal calcium supplements cardiovascular risk did not alter with allocation to calcium and vitamin D. In meta-analyses of three placebo controlled trials, calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.21 (95% confidence interval 1.01 to 1.44), P = 0.04), stroke (1.20 (1.00 to 1.43), P = 0.05), and the composite of myocardial infarction or stroke (1.16 (1.02 to 1.32), P = 0.02). In meta-analyses of placebo controlled trials of calcium or calcium and vitamin D, complete trial-level data were available for 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements. In total 1384 individuals had an incident myocardial infarction or stroke. Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P = 0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P = 0.009). CONCLUSIONS: Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.

11 Review Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. 2010

Bolland, Mark J / Avenell, Alison / Baron, John A / Grey, Andrew / MacLennan, Graeme S / Gamble, Greg D / Reid, Ian R. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand. ·BMJ · Pubmed #20671013.

ABSTRACT: OBJECTIVE: To investigate whether calcium supplements increase the risk of cardiovascular events. DESIGN: Patient level and trial level meta-analyses. DATA SOURCES: Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010. STUDY SELECTION: Eligible studies were randomised, placebo controlled trials of calcium supplements (>or=500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates. RESULTS: 15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038). CONCLUSIONS: Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

12 Review Does calcium supplementation increase cardiovascular risk? 2010

Reid, Ian R / Bolland, Mark J / Grey, Andrew. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz ·Clin Endocrinol (Oxf) · Pubmed #20184602.

ABSTRACT: Calcium supplementation is widely used for the prevention of osteoporosis in postmenopausal women and in men. While there has been ongoing debate regarding its effectiveness in fracture prevention, the underlying assumption has been that, even if it was not particularly effective, at least it was safe. The recent finding of the Auckland Calcium Study that myocardial infarctions were more common in women randomised to calcium calls this assumption into question, and consideration of vascular event data from other calcium trials does not refute the Auckland findings. Meta-analyses of these data will be necessary to settle this matter. It is already accepted that calcium supplements increase vascular risk in patients with renal compromise, even in those not yet requiring dialysis. Also, there is substantial epidemiological evidence that serum calcium levels in the upper part of the normal range are a risk factor for vascular disease, and that calcium supplements acutely elevate serum calcium - a combination of findings that lends plausibility to supplementation increasing vascular risk. As there are reasonable grounds for doubting the safety of calcium supplements, and as the evidence for their efficacy in fracture prevention remains marginal, we suggest that there should be a reappraisal of their role in the management of osteoporosis, with a greater emphasis on agents known to prevent fractures.

13 Review Thiazolidinedione-induced skeletal fragility--mechanisms and implications. 2009

Grey, Andrew. ·Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz ·Diabetes Obes Metab · Pubmed #18671797.

ABSTRACT: Recent evidence suggests that the risk of several types of fracture is increased in type 2 diabetes mellitus (T2DM). Thiazolidinediones (TZDs) are now widely used in the management of T2DM, and their use may increase in other diseases characterized by insulin resistance. The PPAR-gamma, the molecular target of the TZDs currently in clinical use, is expressed in skeletal tissue. Evidence from preclinical studies has demonstrated that activation of PPAR-gamma (i) inhibits bone formation by diverting mesenchymal stem cells from the osteogenic to the adipocytic lineage and (ii) may increase bone resorption by stimulating the development of osteoclasts. There is also potential for indirect adverse skeletal effects of PPAR-gamma activation by modulation of circulating levels of hormones and cytokines known to influence bone metabolism. Recent studies in humans have demonstrated that TZDs decrease markers of bone formation decrease bone mass, and increase fracture rates, at least in women. The implication of these findings is that fracture risk should be considered in patients with T2DM for whom TZD therapy is being considered, and appropriate therapy instigated to prevent fractures in individuals ascertained to be at high risk.

14 Review Effect of calcium supplementation on hip fractures. 2008

Reid, I R / Bolland, M J / Grey, A. ·Faculty of Medical and Health Sciences, University of Auckland, Private Bag, 92019 Auckland, New Zealand. i.reid@auckland.ac.nz ·Osteoporos Int · Pubmed #18286218.

ABSTRACT: There have been numerous studies of the effects of calcium supplementation, with or without vitamin D, on fractures. Individually, they have not provided clarity regarding calcium's anti-fracture efficacy, though they have established that calcium does have beneficial effects on bone density throughout the skeleton in women. Meta-analysis of these data suggests that total fracture numbers are diminished. However, the data from the 5,500 women involved in trials of calcium monotherapy show consistent adverse trends in numbers of hip fractures (relative risk 1.50, 95% CI 1.06-2.12). Observational data from the Study of Osteoporotic Fractures show a similar increase in risk of hip fracture associated with calcium use. We hypothesize that reduced periosteal expansion in women using calcium supplementation might account for the differences in anti-fracture efficacy of calcium at the hip, in comparison with other sites. Until there are further trial results to clarify this area, the present findings suggest that reliance on high calcium intakes to reduce the risk of hip fracture in older women is not appropriate. In addition, those at risk should be looking to other agents with a proven capacity to prevent hip fractures, such as bisphosphonates.

15 Article Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial. 2017

Grey, Andrew / Bolland, Mark J / Horne, Anne / Mihov, Borislav / Gamble, Greg / Reid, Ian R. ·Department of Medicine, University of Auckland, Auckland, New Zealand a.grey@auckland.ac.nz. · Department of Medicine, University of Auckland, Auckland, New Zealand. ·CMAJ · Pubmed #28893875.

ABSTRACT: BACKGROUND: Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain. METHODS: We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover. RESULTS: The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI -1.1% to 5.0%), 2.2% (95% CI -1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI -0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2-3 years in the 1-mg group, 3-4 years in the 2.5-mg group and at least 5 years in the 5-mg group. INTERPRETATION: The antiresorptive activity of single zoledronate doses of 1-5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended. TRIAL REGISTRATION: www.anzctr.org.au, no. ACTRN12607000576426.

16 Article The Impact of 3-D Models versus Animations on Perceptions of Osteoporosis and Treatment Motivation: A Randomised Trial. 2017

Jones, Annie S K / Fernandez, Justin / Grey, Andrew / Petrie, Keith J. ·Department of Psychological Medicine, University of Auckland, Auckland, New Zealand. · Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Psychological Medicine, University of Auckland, Auckland, New Zealand. kj.petrie@auckland.ac.nz. ·Ann Behav Med · Pubmed #28474286.

ABSTRACT: BACKGROUND: Osteoporosis is a degenerative bone disorder that disproportionately affects older women worldwide. Raising awareness regarding osteoporosis within this demographic is significant for health promotion. Initial evidence suggests that visualisations of illness and treatment can improve illness perceptions, increase treatment motivations and even promote health behaviours. We are yet to understand whether different visualisation mediums vary in their impact on perceptions and motivations. PURPOSE: We investigated whether physical models or virtual animations had a greater impact on changing perceptions of osteoporosis and treatment motivation in an at-risk population of older women. METHODS: A total of 128 women aged 50 and over were randomly assigned to view a brief presentation about osteoporosis using either 3-D printed bone models or electronic tablet animations. Illness perceptions, medication beliefs and motivations were measured at baseline and post-presentation. Mixed ANOVAs were used to identify significant changes over time between groups. RESULTS: There were no significant interaction effects, revealing that neither medium had a greater impact on beliefs over time. Significant main effects of time revealed that from baseline to post-presentation, both mediums increased consequence beliefs, personal and treatment control, understanding of osteoporosis, motivations to take treatment if needed and medication necessity beliefs. Timeline beliefs and medication concerns decreased over time for both groups. CONCLUSIONS: Both 3-D models and animations of osteoporosis are equally effective in changing beliefs and treatment motivation in an at-risk population. Visualisation devices are brief, cost-effective, have high acceptability and have considerable clinical applicability to promote awareness and prevention.

17 Article Randomised trial assessing the impact of framing of fracture risk and osteoporosis treatment benefits in patients undergoing bone densitometry. 2017

Kalluru, Rama / Petrie, Keith J / Grey, Andrew / Nisa, Zaynah / Horne, Anne M / Gamble, Greg D / Bolland, Mark J. ·Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Rheumatology, Greenlane Clinical Centre, Auckland, New Zealand. · Department of Psychological Medicine, University of Auckland, Auckland, New Zealand. ·BMJ Open · Pubmed #28188155.

ABSTRACT: OBJECTIVES: The accuracy of patients' perception of risk is important for decisions about treatment in many diseases. We framed the risk of fracture and benefits of treatment in different ways and assessed the impact on patients' perception of fracture risk and intentions to take medication. DESIGN: Randomised trial of 4 different presentations of fracture risk and likely benefits from osteoporosis treatment. SETTING: Academic centre. PARTICIPANTS: 200 patients undergoing bone densitometry. INTERVENTION: Presentation that framed the patient's absolute fracture risk either as the chance of having or not having an event, with their likely benefits from osteoporosis treatment in natural frequencies or numbers needed to treat. OUTCOMES: Participants' views about their fracture risk and the need for osteoporosis treatment. RESULTS: The median 5-year fracture risk threshold participants regarded as high enough to consider preventative medication was 50-60%, and did not change substantially after the presentation. The median (Q1, Q3) 5-year risk initially estimated by participants was 20% (10, 50) for any fracture and 19% (10, 40) for hip fracture. 61% considered their fracture risk was low or very low, and 59-67% considered their fracture risk was lower than average. These participant estimates were 2-3 times higher than Garvan calculator estimates for any fracture, and 10-20 times higher for hip fracture. Participant estimates of fracture risk halved after the presentation, but remained higher than the Garvan estimates (1.5-2 times for any fracture, 5-10 times for hip fracture). There was no difference in these outcomes between the randomised groups. Participants' intentions about taking medication to prevent fractures were not substantially affected by receiving information about fracture risk and treatment benefits. CONCLUSIONS: Altering the framing of estimated fracture risks and treatment benefits had little effect on participants' perception of the need to take treatment or their individual fracture risk. TRIAL REGISTRATION NUMBER: ACTRN12613001081707; Pre-results.

18 Article Ten years too long: strontium ranelate, cardiac events, and the European Medicines Agency. 2016

Bolland, Mark J / Grey, Andrew. ·Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand m.bolland@auckland.ac.nz. · Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand. ·BMJ · Pubmed #27694477.

ABSTRACT: -- No abstract --

19 Article Outcomes of bone density measurements in coeliac disease. 2016

Bolland, Mark J / Grey, Andrew / Rowbotham, David S. ·Bone and Joint Research Group, Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. m.bolland@auckland.ac.nz. ·N Z Med J · Pubmed #26914297.

ABSTRACT: AIM: Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. METHODS: We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' RESULTS: Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. CONCLUSIONS: Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

20 Article Management recommendations for osteoporosis in clinical guidelines. 2016

Wang, Michael / Bolland, Mark / Grey, Andrew. ·Department of Medicine, University of Auckland, Auckland, New Zealand. ·Clin Endocrinol (Oxf) · Pubmed #26668071.

ABSTRACT: OBJECTIVE: Numerous guidelines advise about management of osteoporosis, but little research has been conducted on their recommendations. We analysed recommendations on management of bone health in clinical guidelines. DESIGN: We surveyed recommendations on assessment, treatment and monitoring of bone health in 78 clinical guidelines (22 primary focus osteoporosis, 56 primary focus not osteoporosis) lodged at the Agency for Health Research and Quality National Guidelines Clearinghouse between 1/1/2009 and 12/31/2014. MEASUREMENTS: Governance of guidelines; discussion of fracture risk in the target population; recommendations for assessment, treatment and monitoring of bone health. RESULTS: Only 14% of guidelines discussed fracture risk in the target population. When guidelines discussed assessment, 98% recommended bone mineral density (BMD) measurement but only 27% recommended estimation of fracture risk. When guidelines discussed treatment, 63-71% recommended calcium and/or vitamin D, while <12% recommended avoiding low body weight or smoking cessation. When guidelines discussed intervention, 53% did so on the basis of BMD measurement, and only 27% on the basis of estimated fracture risk. When guidelines discussed monitoring, >90% recommended BMD measurements, and only 3% recommended estimation of fracture risk. About 65% of guidelines that suggested a BMD monitoring interval recommended one of ≤3 years. Compared to guidelines with a primary focus on osteoporosis, guidelines whose primary focus was not osteoporosis were less likely to discuss fracture risk in the target population (2% vs 45%), recommend estimation of fracture risk (11% vs 55%) and recommend intervention on the basis of estimated fracture risk (10% vs 67%) (all P < 0·005). CONCLUSIONS: Our findings highlight a strong focus in clinical guidelines on BMD, a surrogate measure, rather than fracture risk, the clinically important outcome, particularly when bone health is not the primary focus. Addressing this issue might facilitate more rational use of resources and improve patient care.

21 Article 3-D bone models to improve treatment initiation among patients with osteoporosis: A randomised controlled pilot trial. 2016

Stephens, Melika H / Grey, Andrew / Fernandez, Justin / Kalluru, Ramanamma / Faasse, Kate / Horne, Anne / Petrie, Keith J. ·a Department of Psychological Medicine , University of Auckland , Auckland , New Zealand. · b Department of Medicine , University of Auckland , Auckland , New Zealand. · c Auckland Bioengineering Institute , University of Auckland , Auckland , New Zealand. · d Faculty of Medical and Health Sciences, Psychological Medicine , University of Auckland , Auckland , New Zealand. ·Psychol Health · Pubmed #26513581.

ABSTRACT: OBJECTIVE: To investigate the efficacy of 3-D printed bone models as a tool to facilitate initiation of bisphosphonate treatment among individuals who were newly diagnosed with osteoporosis. DESIGN: Fifty eight participants with estimated fracture risk above that at which guidelines recommend pharmacological intervention were randomised to receive either a standard physician interview or an interview augmented by the presentation of 3-D bone models. MAIN OUTCOME MEASURES: Participants' beliefs about osteoporosis and bisphosphonate treatment, initiation of bisphosphonate therapy assessed at two months using self-report and pharmacy dispensing data. RESULTS: Individuals in the 3-D bone model intervention condition were more emotionally affected by osteoporosis immediately after the interview (p = .04) and reported a greater understanding of osteoporosis at follow-up (p = .04), than the control group. While a greater proportion of the intervention group initiated an oral bisphosphonate regimen (alendronate) (52%) in comparison with the control group (21%), the overall initiation of medication for osteoporosis, including infusion (zoledronate), did not differ significantly (intervention group 62%, control group 45%, p = .19). CONCLUSION: The presentation of 3-D bone models during a medical consultation can modify cognitive and emotional representations relevant to treatment initiation among people with osteoporosis and might facilitate commencement of bisphosphonate treatment.

22 Article Web of industry, advocacy, and academia in the management of osteoporosis. 2015

Grey, Andrew / Bolland, Mark. ·Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand a.grey@auckland.ac.nz. · Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. ·BMJ · Pubmed #26198274.

ABSTRACT: -- No abstract --

23 Article Bone density in healthy men after cessation of calcium supplements: 20-month follow-up of a randomized controlled trial. 2015

Kalluru, R / Ames, R / Mason, B / Bolland, M J / Gamble, G D / Grey, A / Horne, A / Reid, I R. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. ·Osteoporos Int · Pubmed #25231677.

ABSTRACT: INTRODUCTION: Calcium supplements, or supplements of calcium-rich foods, have a positive effect on bone mineral density (BMD). However, it is uncertain whether there are any residual benefits of calcium on BMD following cessation of supplementation. METHODS: In a previously published study, 323 healthy men were randomized to receive elemental calcium 600 mg/day (n = 108), calcium 1,200 mg/day (n = 108), or placebo (n = 107) over 2 years. Consenting men from the placebo and calcium 1,200 mg/day groups (85 and 87, respectively) were followed over the next 1-2 years (mean 20 months), off trial medication. RESULTS: In the core trial, BMD increased at all sites by 1.0-1.5% at 2 years in the group receiving calcium 1,200 mg/day, compared to the group receiving placebo. In post-trial follow-up, the calcium group has some residual benefit at the total body (0.41% above placebo; P = 0.04) but there was no significant between-group differences at other sites. CONCLUSION: Following cessation of calcium supplements in healthy men, there is a small residual benefit in total body BMD, but not at the hip or spine. This is unlikely to confer a clinically significant dividend in terms of ongoing fracture prevention.

24 Article The Auckland calcium study: 5-year post-trial follow-up. 2014

Radford, L T / Bolland, M J / Mason, B / Horne, A / Gamble, G D / Grey, A / Reid, I R. ·Department of Medicine, University of Auckland, Auckland, New Zealand. ·Osteoporos Int · Pubmed #24114400.

ABSTRACT: INTRODUCTION: The Auckland calcium study was a 5-year randomised controlled trial of 1 g/day calcium citrate in 1,471 postmenopausal women. Calcium did not reduce total, vertebral or forearm fracture incidence, increased hip fracture incidence and had beneficial effects on bone mineral density (BMD). A secondary analysis raised concerns about the cardiovascular safety of calcium. The purpose of this study was to determine whether the effects of calcium on fracture incidence, BMD and cardiovascular endpoints persisted after supplement discontinuation. METHODS: Approximately 5-years post-trial, we collected information on the 1,408 participants alive at trial completion from the national databases of hospital admissions and deaths. We contacted 1,174 women by phone, and from these we obtained information on medical events and post-trial calcium use. We undertook BMD measurements at 10 years in a selected subset of 194 women who took study medication for 5 years in the original trial, and did not take bone-active medications post-trial. RESULTS: Over the 10-year period, there was no effect on total fracture (HR 0.90, 95% CI 0.75-1.07) or hip fracture incidence (1.40, 0.89-2.21), but significant reductions in forearm (0.62, 0.43-0.89) and vertebral fractures (0.52, 0.32-0.85) in those assigned to calcium. There were no between-group differences in BMD at 10 years at any site. The adverse cardiovascular outcomes observed in the 5-year trial did not persist post-trial. CONCLUSION: Calcium supplementation for 5 years had no effect on total fracture incidence at 10 years. The positive benefits on BMD and the adverse cardiovascular effects did not persist once supplements were stopped.

25 Article Duration of antiresorptive effects of low-dose zoledronate in osteopenic postmenopausal women: a randomized, placebo-controlled trial. 2014

Grey, Andrew / Bolland, Mark / Mihov, Bobby / Wong, Sumwai / Horne, Anne / Gamble, Greg / Reid, Ian R. ·Department of Medicine, University of Auckland, Auckland, New Zealand. ·J Bone Miner Res · Pubmed #23761303.

ABSTRACT: Annual intravenous administration of 5 mg zoledronate decreases fracture risk, but the optimal dosing regimen for zoledronate has not been determined. We set out to evaluate the antiresorptive effects of a single administration of lower doses of zoledronate. A total of 180 postmenopausal women with osteopenia enrolled in a double-blind, randomized, placebo-controlled trial over 2 years at an academic research center. Participants were randomized to a single baseline administration of intravenous zoledronate in doses of 1 mg, 2.5 mg, or 5 mg, or placebo. The primary endpoint was change in bone mineral density(BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body, and changes in biochemical markers of bone turnover. After 2 years, the change in spine BMD was greater in each of the zoledronate groups than in the placebo group; values are mean (95% confidence interval [CI]) difference versus placebo: zoledronate 1 mg 4.4% [2.7% to 6.1%]; 2.5 mg 5.5% [3.9% to 7.2%]; 5 mg 5.3% [3.8% to 6.7%], p < 0.001 for each dose). Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group (mean [95% CI] difference versus placebo: zoledronate 1 mg 2.6% [1.5% to 3.7%]; 2.5 mg 4.4% [3.5% to 5.3%]; 5 mg 4.7% [3.7% to 5.7%], p < 0.001 for each dose). Each of the bone turnover markers, β-C-terminal telopeptide of type I collagen (β-CTX) and procollagen type-I N-terminal propeptide (P1NP), was lower in each of the 2.5-mg and 5-mg zoledronate groups than the placebo group throughout the trial (p < 0.001 versus placebo for each marker for each dose at each time point). For each endpoint, changes were similar in the 2.5-mg and 5-mg zoledronate groups, whereas those in the 1-mg group were smaller than those in the other zoledronate groups. These data demonstrate that single administrations of zoledronate 1 mg or 2.5 mg produce antiresorptive effects that persist for at least 2 years. Trials assessing the antifracture efficacy of intermittent low doses of zoledronate, in particular the 2.5-mg dose, are justified.