Ian R Reid

University of Auckland, Окленд, Auckland, New Zealand

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Publications (463)3117.67 Total impact

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    ABSTRACT: Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. Introduction: Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. Methods: We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. Results: T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = −0.32, p = 0.05) and 8 h (r = −0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). Conclusions: These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification. © 2015 International Osteoporosis Foundation and National Osteoporosis Foundation
    No preview · Article · Oct 2015 · Osteoporosis International
  • M J Bolland · A Grey · I R Reid
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    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.
    No preview · Article · Oct 2015 · Climacteric
  • I. R. Reid

    No preview · Article · Oct 2015 · Osteoporosis International
  • Ian R Reid
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    ABSTRACT: Our understanding of bone biology and the subsequent development of therapies to treat bone diseases have both expanded greatly in the past 30 years. This article reviews some of the key advances made in these fields during the past decade.
    No preview · Article · Aug 2015 · Nature Reviews Endocrinology
  • Ian R Reid
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    ABSTRACT: The classical clinical consequence of vitamin D deficiency is osteomalacia, presenting as rickets in children. This remains a common problem in parts of the Middle East and the Indian subcontinent, and occurs when serum 25-hydroxyvitamin D levels are <25 nmol/L. Osteomalacia remains the only problem that is unequivocally a consequence of vitamin D deficiency. Low levels of 25-hydroxyvitamin D are observed in a wide range of conditions, but consistent trial evidence of amelioration of these conditions with vitamin D is lacking. Monotherapy with vitamin D has not been found to be effective in meta-analyses of trials assessing its effects on bone density, fractures or falls. At present, supplements should be advised for individuals at risk of having serum 25-hydroxyvitamin D levels in the 25-40 nmol/L range, or below, with a view to prevention of osteomalacia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Jul 2015 · Archives of Disease in Childhood

  • No preview · Article · Jun 2015 · The Journal of Clinical Endocrinology and Metabolism
  • Ian R Reid
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    ABSTRACT: Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <-2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies.
    No preview · Article · May 2015 · Nature Reviews Endocrinology
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    ABSTRACT: While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly−Pivotal Fracture Trial (HORIZON−PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was −0.54% in Z9 vs. −1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: −0.37%, 1.93%; p = 0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. © 2015 American Society for Bone and Mineral Research.
    No preview · Article · May 2015 · Journal of Bone and Mineral Research

  • No preview · Article · May 2015 · The Journal of Clinical Endocrinology and Metabolism

  • No preview · Article · Apr 2015 · The Journal of Clinical Endocrinology and Metabolism
  • 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.
    No preview · Article · Dec 2014 · Journal of Internal Medicine
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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.
    Preview · Article · Nov 2014 · Journal of Clinical Endocrinology & Metabolism

  • No preview · Conference Paper · Nov 2014

  • No preview · Conference Paper · Nov 2014
  • I. R. Reid

    No preview · Article · Oct 2014 · Revista Clínica Española
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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.
    No preview · Article · Sep 2014 · Journal of Clinical Endocrinology & Metabolism
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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 %. We prospectively investigated the incidence of ocular side effects after a single intravenous zoledronate infusion. In a secondary analysis of a double-blind, placebo-controlled trial in which early post-menopausal women (N = 1054) with normal bone density or osteopenia were randomized to infusion of zoledronate 5 mg (N = 703) or placebo (N = 351), we analyzed significant adverse ocular events occurring within 3 months. Fourteen participants reported ocular symptoms after the infusion. All were examined by an ophthalmologist and eight were diagnosed with acute anterior uveitis (AAU) and one with sectoral episcleritis. The incidence of AAU and episcleritis was 1.1 % (95 % CI 0.5-2.1) and 0.1 % (95 % CI 0.0-0.7), respectively, in the zoledronate group and 0 % for both conditions in the placebo group (95 % CI 0.0-0.8). The mean time from infusion to symptom onset for AAU was 3 days (range 2-4). Three cases were bilateral. AAU was mild-moderate in seven participants and severe in one. All affected eyes were treated with topical cyclopentolate 1 % (to break, or minimize, posterior synechiae), and intensive, potent, topical corticosteroids with a tapering regime based on treatment response. The mean duration of topical corticosteroid was 26 +/- 10 days (range 17-44). The mean, best corrected visual acuity was 20/20 (range 20/20-20/40) at presentation, which remained unchanged after AAU resolution. None of the participants lost vision, and no long-term sequelae were reported at last follow-up (range 3-13 months post-infusion). Prescribers should inform patients about the possibility of ocular side effects with zoledronate infusions and refer promptly to an ophthalmologist if symptoms develop.
    No preview · Article · Sep 2014 · Osteoporosis International
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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
    No preview · Article · Sep 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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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.
    No preview · Article · Sep 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: 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
    No preview · Article · Aug 2014 · Osteoporosis International

Publication Stats

23k Citations
3,117.67 Total Impact Points


  • 1970-2015
    • University of Auckland
      • • Department of Medicine
      • • Faculty of Medical and Health Sciences
      Окленд, Auckland, New Zealand
  • 2013
    • University of Southampton
      Southampton, England, United Kingdom
  • 2011
    • Auckland District Health Board
      Окленд, Auckland, New Zealand
  • 1992-2009
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 2008
    • University of Otago
      Taieri, Otago Region, New Zealand
  • 2007
    • New Mexico Clinical Research and Osteoporosis Center
      Albuquerque, New Mexico, United States
  • 2005
    • Duke University
      Durham, North Carolina, United States
  • 2004
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2003
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1995-1996
    • Auckland City Hospital
      Окленд, Auckland, New Zealand
  • 1987-1989
    • 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