Ian R Reid

John Wayne Cancer Institute, Santa Monica, California, United States

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Publications (424)2751.61 Total impact

  • The Journal of Clinical Endocrinology and Metabolism 04/2015; 100(4):L36. DOI:10.1210/jc.2015-1568 · 6.31 Impact Factor
  • Ian R Reid
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    ABSTRACT: 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 anti-fracture 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, non-spine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and non-spine 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 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 12/2014; DOI:10.1111/joim.12339 · 5.79 Impact Factor
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    ABSTRACT: Objective: The aim of this guideline was to formulate practice guidelines for the diagnosis and treatment of Paget's disease of the bone. Participants: The guideline was developed by an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. Conclusions: We recommend that plain radiographs be obtained of the pertinent regions of the skeleton in patients with suspected Paget's disease. If the diagnosis is confirmed, we suggest that a radionucleotide bone scan be done to determine the extent of the disease. After diagnosis of Paget's disease, we recommend measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients. We suggest treatment with a bisphosphonate for most patients with active Paget's disease who are at risk for future complications. We suggest a single 5-mg dose of iv zoledronate as the treatment of choice in patients who have no contraindication. In patients with monostotic disease who have a normal serum total alkaline phosphatase, we suggest that a specific marker of bone formation and bone resorption be measured, although these may still be normal. Serial radionuclide bone scans may determine the response to treatment if the markers are normal. We suggest that bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget's disease and may reverse paraplegia associated with spinal Paget's disease. We suggest treatment with a bisphosphonate before surgery on pagetic bone.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; DOI:10.1210/jc.2014-2910 · 6.31 Impact Factor
  • I. R. Reid
    Revista Clínica Española 10/2014; 214(7). DOI:10.1016/j.rce.2014.05.015 · 1.31 Impact Factor
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    ABSTRACT: Context: Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period. Objective: To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups. Design: 3 year extension of HORIZON. Setting: Multicenter trial. Participants: 1233 women who previously received 3 ZOL treatments during Core trial. Intervention: Randomization to 3 additional annual ZOL (Z6, n=616) or placebo infusions (Z3P3, n=617). Main Outcomes: Risk of Morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF). Results: Incidence of MorphVertFx in Z3P3 was predicted by: Femoral Neck (FN) T-score ≤-2.5 [OR 3.3(1.4, 8.0), p=0.008], Total Hip (TH) T-score ≤-2.5 [OR 4.0(1.8, 9.0), p=0.0007], and incident MorphVertFx during Core [OR 4.75(1.4, 16.8), p<0.015]. Incidence of NVF was predicted by TH T-score [for 1 decline, HR 1.7(1.2, 2.6), p=0.008], incident NVF during Core [HR 2.5(1.2, 5.3), p=0.014], and prevalent vertebral fracture [HR 3.0(1.4, 6.3), p=0.005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions. Conclusions: After 3 years of ZOL, in women who have a TH T-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture is low if treatment is discontinued (for MorphVertFx average risk 3.2%, range 2.8-3.8% for subgroups, and for NVF average risk 5.8%, range 1.1-8.8% for subgroups). In these patients, discontinuation for up to 3 years is reasonable.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; DOI:10.1210/jc.2014-1971 · 6.31 Impact Factor
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    ABSTRACT: This prospective study showed that the incidence of acute anterior uveitis, confirmed by ophthalmic examination, in patients receiving intravenous zoledronate infusions as part of a randomized controlled trial for fracture prevention is 1.1 %.
    Osteoporosis International 09/2014; DOI:10.1007/s00198-014-2872-5 · 4.17 Impact Factor
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    ABSTRACT: Several studies have shown that high bone turnover is associated with 1) greater rates of bone loss and 2) greater BMD response to anti-resorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss prior to therapy are associated with greater BMD response to anti-resorptive therapy. In the HORIZON-PFT study and its extension, one group of women who were randomized to receive placebo for 3 years (years 1, 2 and 3), were then switched to ZOL 5 mg annually for up to three injections (years 4, 5 and 6, P3Z3 arm) (n = 1223). We measured total hip BMD at baseline, 1, 2 and 3 years on placebo and at 4.5 and 6 years on ZOL. The PINP was measured at 3, 4.5 and 6 years. By design, not all subjects were followed for as long as 6 years, so this analysis focused on the results at 4.5 years. Those with the largest loss in total hip BMD during PBO in years 0-3 had largest gain during ZOL (years 3 to 4.5): (r= -0.39, p < 0.0001). The change in total hip BMD in years 0-3 on placebo was related to the serum PINP at the end of the 3-year period (r= -0.24, P < 0.0001). The change in total hip BMD on ZOL from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r= 0.26, P < 0.0001). We conclude that BMD response to ZOL is greater in postmenopausal women who had larger loss prior to treatment. This association may result from higher bone turnover being associated with both greater bone loss on placebo and greater BMD response to ZOL. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2014; 30(3). DOI:10.1002/jbmr.2361 · 6.59 Impact Factor
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    ABSTRACT: Denosumab reduced bone resorption, increased BMD, and decreased new vertebral, hip, and nonvertebral fracture risk in postmenopausal women with osteoporosis in the FREEDOM trial. Consistent with its mechanism of action, transiliac crest bone biopsies from subjects treated with denosumab for 1 to 3 years demonstrated reduced bone turnover that was reversible upon treatment cessation. Long-term denosumab treatment for up to 6 years in the FREEDOM extension provides sustained bone turnover reduction and continued low fracture incidence. Here we evaluate 5 years of denosumab treatment on bone remodeling at the tissue level. Transiliac crest bone biopsies were obtained from 41 subjects (13 cross-over and 28 long-term from the FREEDOM placebo and denosumab groups, respectively) at year 2 of the FREEDOM extension, representing up to 5 years of denosumab treatment. Demographics for this subset were comparable to the overall extension cohort. The mean (SD) duration from the last denosumab dose to the first dose of tetracycline was 5.7 (0.5) months. Qualitative bone histology assessed in all biopsy samples was unremarkable, showing normally mineralized lamellar bone. Structural indices, including trabecular bone volume, number, and surface, were similar between cross-over and long-term groups. Bone resorption was decreased as reflected by eroded surface in cross-over and long-term subjects. A total of 11/13 (85%) cross-over subjects and 20/28 (71%) long-term subjects had specimens with double or single tetracycline label in trabecular and/or cortical compartments; specimens from 5 cross-over subjects and 10 long-term subjects were evaluable for dynamic trabecular bone parameters. Dynamic remodeling indices were low for both groups and consistent with reduced bone turnover with denosumab. In conclusion, denosumab treatment through 5 years resulted in normal bone quality with reduced bone turnover. These observations are consistent with its mechanism of action and associated with continued BMD increases and low fracture incidence. © 2014 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2014; 29(9). DOI:10.1002/jbmr.2236 · 6.59 Impact Factor
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    ABSTRACT: Summary Small studies have previously suggested that sarcoidosis may be associated with low bone mineral density. In this observational study of 64 patients with sarcoidosis, bone mineral density was within the normal range at baseline, and there was no evidence of accelerated bone loss over 1-2 years. Introduction Several small studies have suggested that sarcoidosis may be associated with low bone mineral density (BMD). Methods We undertook a cross-sectional study of BMD in 64 patients with sarcoidosis. Of these, 27 with 25-hydroxyvitamin D Results The mean age of participants was 58 years, 68 % were female, and 8 % were currently using oral glucocorticoids. At baseline, BMD for the entire cohort was greater than the expected values for the population at the lumbar spine (mean Z-score 0.7, P P P = 0.14) and total hip (0.2, P = 0.14). BMD did not change at any of these four sites (P > 0.19) over 2 years in the longitudinal study. In the intervention study, vitamin D supplements had no effect on BMD, and therefore we pooled the data from all participants. BMD did not change over 1 year at the spine, total hip, or femoral neck (P > 0.3), but decreased by 0.7 % (95 % confidence interval 0.3-1.1) at the total body (P = 0.019). Conclusions BMD was normal at baseline, and there was no consistent evidence of accelerated bone loss over 1-2 years, regardless of baseline vitamin D status. Patients with sarcoidosis not using oral glucocorticoids do not need routine monitoring of BMD.
    Osteoporosis International 08/2014; 26(2). DOI:10.1007/s00198-014-2870-7 · 4.17 Impact Factor
  • Ian R Reid
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    ABSTRACT: Of late, clinical trial data, meta-analyses and observational studies have caused concern that the use of calcium supplements might increase the risk of myocardial infarction and stroke. A new meta-analysis suggests that there is no problem with calcium supplements, but as the analysis includes controversial data omitted from previous analyses, the debate will continue.
    Nature Reviews Endocrinology 08/2014; 10(11). DOI:10.1038/nrendo.2014.146 · 12.96 Impact Factor
  • I R Reid, M J Bolland
    Osteoporosis International 08/2014; 25(10). DOI:10.1007/s00198-014-2842-y · 4.17 Impact Factor
  • Clinical Chemistry 07/2014; DOI:10.1373/clinchem.2014.222521 · 7.77 Impact Factor
  • Ian R Reid
    Journal of endocrinological investigation 07/2014; DOI:10.1007/s40618-014-0127-0 · 1.55 Impact Factor
  • I R Reid, M J Bolland
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    ABSTRACT: The vitamin D endocrine system is critical for the maintenance of circulating calcium concentrations, but recently, there has been advocacy for the widespread use of vitamin D supplements to improve skeletal and nonskeletal health. Recent studies of tissue-selective vitamin D receptor knockout mice indicate that the principal action of vitamin D responsible for the maintenance of calcium homoeostasis is the regulation of intestinal calcium absorption. High levels of vitamin D can increase bone resorption and impair mineralization, consistent with its role in maintaining circulating calcium concentrations. These findings suggest that circumspection is appropriate in its clinical use. There is now substantial clinical trial data with vitamin D supplements, which fails to establish their efficacy on bone density or the prevention of falls or fractures. However, some trials in frail and/or vitamin D-deficient populations have produced positive outcomes. Where there are positive effects of vitamin D supplementation on skeletal outcomes, these are mainly seen in cohorts with baseline circulating 25-hydroxyvitamin D (25(OH)D) levels in the range 25-40 nmol/L or lower. A great diversity of nonskeletal conditions have been associated with low 25(OH)D, but there is little evidence for efficacy of vitamin D supplementation for such end-points. At present, supplements should be advised for populations with risk factors (e.g., lifestyle, skin color, and frailty) for having serum 25(OH)D levels in the 25- to 40-nmol/L range or below. A dose of ≤800 IU/day is adequate. This approach will maintain 25(OH)D levels well above the threshold for osteomalacia and makes allowance for the poor accuracy and precision of some 25(OH)D assays.
    Osteoporosis International 05/2014; 25(10). DOI:10.1007/s00198-014-2749-7 · 4.17 Impact Factor
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    Ian R Reid
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    ABSTRACT: Advocacy for the use of calcium supplements arose at a time when there were no other effective interventions for the prevention of osteoporosis. Their promotion was based on the belief that increasing calcium intake would increase bone formation. Our current understandings of the biology of bone suggest that this does not occur, though calcium does act as a weak antiresorptive. Thus, it slows postmenopausal bone loss but, despite this, recent meta-analyses suggest no significant prevention of fractures. In sum, there is little substantive evidence of benefit to bone health from the use of calcium supplements. Against this needs to be balanced the likelihood that calcium supplement use increases cardiovascular events, kidney stones, gastrointestinal symptoms, and admissions to hospital with acute gastrointestinal problems. Thus, the balance of risk and benefit seems to be consistently negative. As a result, current recommendations are to obtain calcium from the diet in preference to supplements. Dietary calcium intake has not been associated with the adverse effects associated with supplements, probably because calcium is provided in smaller boluses, which are absorbed more slowly since they come together with quantities of protein and fat, resulting in a slower gastric transit time. These findings suggest that calcium supplements have little role to play in the modern therapeutics of osteoporosis, which is based around the targeting of safe and effective anti-resorptive drugs to individuals demonstrated to be at increased risk of future fractures.
    02/2014; 21(1):21-28. DOI:10.11005/jbm.2014.21.1.21
  • Ian R Reid, Gregory D Gamble
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    ABSTRACT: There is a wide range of practices regarding times between bone density (BMD) measurements in osteopenic women. If decisions to treat osteoporosis are to be based on absolute fracture risk, then projections of fracture risk are a logical basis for determining appropriate intervals for BMD testing. Fracture risk depends mainly on age and BMD, and bone loss in older women is relatively constant at ∼1% annually, so it is possible to project fracture risk into the future and estimate when an individual's risk will approach the threshold for intervention. Modeling scenarios for a range of osteopenic baseline BMDs in 65 year-old women shows a remarkable consistency in the doubling time for FRAX-assessed fracture risk, of 5-6 years. This estimate is of immediate relevance to clinical practice in that it can be used to determine how long to wait before re-assessing BMD and fracture risk in women whose other risk factors are stable.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2014; 29(2). DOI:10.1002/jbmr.2054 · 6.59 Impact Factor
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    ABSTRACT: The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout. This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies. There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and β-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains. Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.
    Annals of the rheumatic diseases 01/2014; 73(6). DOI:10.1136/annrheumdis-2013-205036 · 9.27 Impact Factor
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    ABSTRACT: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by x-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA, n=14,260), velocity of sound (VOS, n=15,514) and BMD (n=4,566) in 13 discovery cohorts. Independent replication involved 7 cohorts with GWA data (in silico n=11,452) and new genotyping in 15 cohorts (de novo n=24,902). In combined random effects meta-analysis of the discovery and replication cohorts, 9 SNPs had genome-wide significant (p<5×10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708), and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (p<8.23×10(-14)). In meta-analyses involving 25 cohorts with up to 14,985 fracture cases, six of 10 SNPs associated with heel bone properties at p<5×10(-6) also had the expected direction of association with any fracture (p<0.05), including 3 SNPs with p<0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007), and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
    Human Molecular Genetics 01/2014; DOI:10.1093/hmg/ddt675 · 6.68 Impact Factor
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    ABSTRACT: Annual intravenous administration of 5mg zoledronate decreases fracture risk, but the optimal dosing regimen for zoledronate has not been determined. We set out to evaluate the anti-resorptive effects of a single administration of lower doses of zoledronate. 180 postmenopausal women with osteopenia enrolled in a double-blind, randomized, placebo-controlled trial over 2y at an academic research center. Participants were randomized to a single baseline administration of intravenous zoledronate in doses of 1mg, 2.5mg or 5mg, or placebo.The primary endpoint was change in 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 2y, the change in spine BMD was greater in each of the zoledronate groups than in the placebo group [mean (95% CI) difference vs placebo: zoledronate 1mg 4.4% (2.7, 6.1); 2.5mg 5.5% (3.9, 7.2); 5mg 5.3% (3.8, 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 vs placebo: zoledronate 1mg 2.6% (1.5, 3.7); 2.5mg 4.4% (3.5, 5.3); 5mg 4.7% (3.7, 5.7), P < 0.001 for each dose]. Each of the bone turnover markers, β-CTX and P1NP, was lower in each of the 2.5mg and 5mg zoledronate groups than the placebo group throughout the trial (P < 0.001 vs placebo for each marker for each dose at each time point). For each endpoint, changes were similar in the 2.5mg and 5mg zoledronate groups, while those in the 1mg group were smaller than those in the other zoledronate groups. These data demonstrate that single administrations of zoledronate 1mg or 2.5mg produce anti-resorptive effects that persist for at least 2y. Trials assessing the anti-fracture efficacy of intermittent low doses of zoledronate, in particular the 2.5mg dose, are justified.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2014; 29(1). DOI:10.1002/jbmr.2009 · 6.59 Impact Factor
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    ABSTRACT: An analysis of levels of government health research funding carried out in 2008 demonstrated that funding in New Zealand, after adjustment for population size, was less than one-third of that in Australia, less than one-fifth of that in the United Kingdom, and about 10% of that in the United States. This was perceived to be a major obstacle to the recruitment and retention of clinical and academic staff in our hospitals and universities. We have now repeated these analyses to determine the current state of these comparisons. From 2009 to the present funds for direct funding of research through the Health Research Council (HRC) have remained static at $54m. As a result of inflation of research costs (principally salaries) this represents a decrease of approximately one-quarter in the quantum of research funded by the HRC over the last 4 years. Current funding rates in the comparator countries, population-adjusted and converted to NZ$, are 3.4-fold higher in Australia, 4.5-fold higher in the United Kingdom, and 9.7-fold higher in the United States. Urgent and sustained action is needed to correct these major disparities in government health research funding if the quality of academic and clinical staff in our public institutions is to be maintained.
    The New Zealand medical journal 01/2014; 127(1389):25-30.

Publication Stats

17k Citations
2,751.61 Total Impact Points


  • 2014
    • John Wayne Cancer Institute
      Santa Monica, California, United States
  • 1970–2014
    • University of Auckland
      • • Department of Medicine
      • • Faculty of Medical and Health Sciences
      Окленд, Auckland, New Zealand
  • 2013
    • University of Southampton
      Southampton, England, United Kingdom
  • 2005–2009
    • Duke University
      Durham, North Carolina, United States
  • 1992–2009
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 2008
    • University of Otago
      Taieri, Otago Region, New Zealand
    • University of Western Sydney
      • Centre for Complementary Medicine Research (CompleMED)
      Penrith, New South Wales, Australia
  • 2007
    • New Mexico Clinical Research and Osteoporosis Center
      Albuquerque, New Mexico, United States
  • 2004
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2003
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1991–2000
    • Auckland City Hospital
      • Department of Specialist Chemical Pathology
      Auckland, Auckland, New Zealand
  • 1993
    • Middlemore Hospital
      Окленд, Auckland, New Zealand
  • 1987–1991
    • Washington University in St. Louis
      • Division of Bone and Mineral Diseases
      San Luis, Missouri, United States
    • Barnes Jewish Hospital
      • Department of Nephrology
      Saint Louis, MO, United States