{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:29:53Z","timestamp":1775150993529,"version":"3.50.1"},"reference-count":35,"publisher":"BMJ","issue":"6976","license":[{"start":{"date-parts":[[1995,2,11]],"date-time":"1995-02-11T00:00:00Z","timestamp":792460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"accepted":{"date-parts":[[1994,11,25]]},"published-print":{"date-parts":[[1995,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective<\/jats:bold>\n                    : To determine whether alfacalcidol\u2014used in management of overt renal bone disease\u2014may safely prevent renal bone disease when used earlier in course of renal failure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Design<\/jats:bold>\n                    : Double blind, prospective, randomised, placebo controlled study.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Setting<\/jats:bold>\n                    : 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Subjects<\/jats:bold>\n                    : 176 patients aged 18\u201381 with mild to moderate chronic renal failure (creatinine clearance 15\u201350 ml\/min) and with no clinical, biochemical, or radiographic evidence of bone disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Interventions<\/jats:bold>\n                    : Alfacalcidol 0.25 \u03bcg (titrated according to serum calcium concentration) or placebo given for two years.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Main outcome measures<\/jats:bold>\n                    : Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P&lt;0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P&lt;0.001). There was no difference in rate of progression of renal failure between the two groups.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text position=\"float\">\n                      <jats:sec>\n                        <jats:title>Key messages<\/jats:title>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>Key messages<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Treating such patients with alfacalcidol (up to 1 \u03bcg\/day for two years) significantly improved their osteomalacia and hyperparathyroid disease<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Treatment had no apparent adverse effect on renal function<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Hypercalcaemic episodes were uncommon and readily responded to decreases in drug dose<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Alfacalcidol might be used more widely for patients with moderate renal failure not yet needing dialysis<\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:sec>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1136\/bmj.310.6976.358","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T19:33:11Z","timestamp":1319743991000},"page":"358-363","source":"Crossref","is-referenced-by-count":252,"title":["Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure"],"prefix":"10.1136","volume":"310","author":[{"given":"Neveen A T","family":"Hamdy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Kanis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique N C","family":"Beneton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin B","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Job R","family":"Juttmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes G M","family":"Jordans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Josse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Meyrier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L","family":"Lins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian T","family":"Fairey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1995,2,11]]},"reference":[{"key":"2025122508561928000_310.6976.358.1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/ki.1976.42","article-title":"Bone histology in incipient and advanced renal failure.","volume":"9","author":"Malluche","year":"1976","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.2","first-page":"271","volume":"290","author":"Cundy","year":"1985","journal-title":"Who gets renal bone disease before beginning dialysis? BMJ"},{"key":"2025122508561928000_310.6976.358.3","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.26.2.83"},{"key":"2025122508561928000_310.6976.358.4","first-page":"45","article-title":"Correlation of clinical, biochemical and skeletal responses to 1a-hydroxy vitamin D(sub 3) in renal bone disease","volume":"7s","author":"Kanis","year":"1977","journal-title":"Clin Endocrinol"},{"key":"2025122508561928000_310.6976.358.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-351X(88)80013-2"},{"key":"2025122508561928000_310.6976.358.6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/ki.1990.187","article-title":"Renal bone disease 1990: an unmet challenge for the nephrologist.","volume":"38","author":"Malluche","year":"1990","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.7","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1056\/NEJM197205182862009","article-title":"On the pathogenesis of the uremic state. An exposition of the \u201ctrade-off hypothesis.\u201d","volume":"286","author":"Bricker","year":"1972","journal-title":"N Engl J Med"},{"key":"2025122508561928000_310.6976.358.8","first-page":"359","article-title":"The kidney as an endocrine organ for the production of 1,25(OH)(sub 2)D(sub 3), a calcium-mobilising hormone.","volume":"298","author":"DeLuca","year":"1973","journal-title":"N Engl J Med"},{"key":"2025122508561928000_310.6976.358.9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-61-4-601"},{"key":"2025122508561928000_310.6976.358.10","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/ki.1985.220","article-title":"Effect of inorganic phosphate on serum ionised calcium concentrations in vitro: a reassessment of the \u201ctrade-off hypothesis.\u201d","volume":"28","author":"Adler","year":"1985","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.11","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0140-6736(73)92197-1","article-title":"Failure of formation of 1,25-dihydroxycholecalciferol in chronic renal insufficiency.","volume":"i","author":"Mawer","year":"1973","journal-title":"Lancet"},{"key":"2025122508561928000_310.6976.358.12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.7326\/0003-4819-80-2-161","article-title":"1,25 dihydroxyvitamin D(sub 3) in normal man and in patients with renal failure.","volume":"80","author":"Brickman","year":"1974","journal-title":"Ann Intern Med"},{"key":"2025122508561928000_310.6976.358.13","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1172\/JCI111365","article-title":"Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency.","volume":"73","author":"Portale","year":"1984","journal-title":"J Clin Invest"},{"key":"2025122508561928000_310.6976.358.14","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1172\/JCI112666","article-title":"Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.","volume":"78","author":"Lopez-Hilker","year":"1986","journal-title":"J Clin Invest"},{"key":"2025122508561928000_310.6976.358.15","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/ki.1976.60","article-title":"Skeletal resistance to the calcemic action of parathyroid hormone in uremia: Role of 1,25(OH)(sub 2)D(sub 3).","volume":"9","author":"Massry","year":"1975","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.16","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ki.1978.116","article-title":"Resistance to parathyroid hormone in renal failure: role of vitamin D metabolites.","volume":"14","author":"Somerville","year":"1978","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.17","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/ki.1989.89","article-title":"1,25(OH)(sub 2) vitamin D inhibits parathyroid cell proliferation in experimental uraemia.","volume":"35","author":"Szabo","year":"1989","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.18","doi-asserted-by":"publisher","DOI":"10.1210\/endo-117-5-2114"},{"key":"2025122508561928000_310.6976.358.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4270"},{"key":"2025122508561928000_310.6976.358.20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.43.020192.001303"},{"key":"2025122508561928000_310.6976.358.21","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"2025122508561928000_310.6976.358.22","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-65-3-407"},{"key":"2025122508561928000_310.6976.358.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2670(01)84083-6"},{"key":"2025122508561928000_310.6976.358.24","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1600-0609.1992.tb00046.x","article-title":"Abnormal bone histology in patients with myelomatosis and normal biochemical indices of bone resorption.","volume":"49","author":"Taube","year":"1992","journal-title":"Eur J Haematol"},{"key":"2025122508561928000_310.6976.358.25","first-page":"206","article-title":"Histological quantitation of aluminium in iliac bone from patients with renal failure.","volume":"99","author":"Maloney","year":"1982","journal-title":"J Lab Clin Med"},{"key":"2025122508561928000_310.6976.358.26","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1056\/NEJM197705122961901","article-title":"Changes in histologic and biochemical indices of bone turnover after bilateral nephrectomy. Evidence for a possible role of endogenous calcitonin.","volume":"296","author":"Kanis","year":"1977","journal-title":"New Engl J Med"},{"key":"2025122508561928000_310.6976.358.27","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700950209"},{"key":"2025122508561928000_310.6976.358.28","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650020617"},{"key":"2025122508561928000_310.6976.358.29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/ki.1978.90","article-title":"Haemodialysis bone disease: correlation between clinical, histologic and other findings.","volume":"14","author":"Alvarez-Ude","year":"1978","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.30","first-page":"289","article-title":"Treatment of renal bone disease with 1a hydroxylated derivatives of vitamin D(sub 3).","volume":"48","author":"Kanis","year":"1979","journal-title":"Q J Med"},{"key":"2025122508561928000_310.6976.358.31","doi-asserted-by":"crossref","unstructured":"Coburn JW Brickman AS Sherrard DJ Singer FR Baylink DJ Wong EGC .Clinical efficacy of 1,25(OH)(sub 2)D(sub 3) in renal osteodystrophy. In: Norman AW Schaefer K Coburn JW DeLuca HF Fraser D Grigoleit H von Herrath D eds.Vitamin D: biochemical, chemical and clinical aspects relating to calcium metabolism. Berlin: Walter deGruyter,1977: 657\u201366.","DOI":"10.1515\/9783112327203-114"},{"key":"2025122508561928000_310.6976.358.32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000415721","article-title":"Factors modifying the secretion and action of parathyroid hormone in renal failure.","volume":"64","author":"Cundy","year":"1988","journal-title":"Contrib Nephrol"},{"key":"2025122508561928000_310.6976.358.33","first-page":"S62","article-title":"Risk of adynamic bone disease in dialysed patients","volume":"42","author":"Malluche","year":"1992","journal-title":"Kidney Int"},{"key":"2025122508561928000_310.6976.358.34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0140-6736(84)92507-8","article-title":"Plasma creatinine and creatinine clearance in nutritional osteomalacia.","volume":"ii","author":"Fonseca","year":"1984","journal-title":"Lancet"},{"key":"2025122508561928000_310.6976.358.35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212033272305"}],"container-title":["BMJ"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/data.bmj.org\/tdm\/10.1136\/bmj.310.6976.358","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmj.310.6976.358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T16:56:29Z","timestamp":1766681789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.310.6976.358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2,11]]},"references-count":35,"journal-issue":{"issue":"6976","published-online":{"date-parts":[[1995,2,11]]},"published-print":{"date-parts":[[1995,2,11]]}},"alternative-id":["10.1136\/bmj.310.6976.358"],"URL":"https:\/\/doi.org\/10.1136\/bmj.310.6976.358","relation":{},"ISSN":["0959-8138","1468-5833"],"issn-type":[{"value":"0959-8138","type":"print"},{"value":"1468-5833","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2,11]]}}}