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Vitamin D threshold to prevent aromatase inhibitor-related bone loss: the B-ABLE prospective cohort study

  • Epidemiology
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Abstract

Aromatase inhibitor (AI)-related bone loss is associated with increased fracture rates. Vitamin D might play a role in minimising this effect. We hypothesised that 25-hydroxy-vitamin D concentrations [25(OH)D] after 3 months supplementation might relate to bone loss after 1 year on AI therapy. We conducted a prospective cohort study from January 2006 to December 2011 of a consecutive sample of women initiating AI for early breast cancer who were ineligible for bisphosphonate therapy and stayed on treatment for 1 year (N = 232). Serum 25(OH)D was measured at baseline and 3 months, and lumbar spine (LS) bone mineral density at baseline and 1 year. Subjects were supplemented with daily calcium (1 g) and vitamin D3 (800 IU) and additional oral 16,000 IU every 2 weeks if baseline 25(OH)D was <30 ng/ml. Linear regression models were fitted to adjust for potential confounders. After 1 year on AI therapy, 232 participants experienced a significant 1.68 % [95 % CI 1.15–2.20 %] bone loss at LS (0.017 g/cm2 [0.012–0.024], P < 0.0001). Higher 25(OH)D at 3 months protected against LS bone loss (−0.5 % per 10 ng/ml [95 % CI −0.7 to −0.3 %], adjusted P = 0.0001), and those who reached levels ≥40 ng/ml had reduced bone loss by 1.70 % [95 % CI 0.4–3.0 %; adjusted P = 0.005] compared to those with low 25(OH)D levels (<30 ng/ml). We conclude that improved vitamin D status using supplementation is associated with attenuation of AI-associated bone loss. For this population, the current Institute of Medicine target recommendation of 20 ng/ml might be too low to ensure good bone health.

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Acknowledgments

This project has been partially funded by the Instituto Carlos III (FIS Grants 2010, Expedient number PI10/01464). Daniel Prieto-Alhambra receives support from the IDIAP Jordi Gol and Institut Catala de la Salut (“4a Convocatòria d’una estada a una Unitat de Recerca de l’IMIM o de l’ASPB”). The Department of Medical Oncology was supported by “ISCIII/FEDER-Subdirección General de Evaluación y Fomento de la Investigación (PI06 PI10/01464)”, which is part of the “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), iniciativa Ingenio 2010, Programa Consolider”, Instituto de Salud Carlos III/FEDER, Spain (RD06/0020/0109; RD06/0020/0019). The Internal Medicine Department and the URFOA IMIM receive support from the RETICEF (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Instituto Carlos III, Government of Spain). Dr MK Javaid and Professor NK Arden receive support from the NIHR (National Institute of Health Research), Musculoskeletal BRU, Oxford. The authors thank Isabel Aymar for her technical assistance in the DXA measurements.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. URFOA-IMIM, Parc de Salut Mar, Parc de Recerca Biomèdica de Barcelona, C/Dr Aiguader, 88, 2nd Floor, 08003, Barcelona, Spain

    Daniel Prieto-Alhambra, Adolfo Diez-Perez & Xavier Nogues

  2. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, Oxford, OX3 7LD, UK

    Daniel Prieto-Alhambra, M. Kassim Javaid, Nigel K. Arden & Cyrus Cooper

  3. IDIAP Jordi Gol, Unitat de Suport a la Recerca Barcelona, Institut Català de la Salut, Av. Gran Via de les Corts Catalanes, 587 Àtic, 08007, Barcelona, Spain

    Daniel Prieto-Alhambra

  4. Medicine Department, Universitat Autònoma de Barcelona Edificio W – UD de Medicina de la Vall d’Hebron Paseo Vall d’Hebron, 119, 08035, Barcelona, Spain

    Daniel Prieto-Alhambra, Sonia Servitja, Joan Albanell, Ignasi Tusquets, Adolfo Diez-Perez & Xavier Nogues

  5. RETICEF (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad), Instituto Carlos III, Madrid, Spain

    Daniel Prieto-Alhambra, Adolfo Diez-Perez & Xavier Nogues

  6. Oncology Department, Parc de Salut Mar, Barcelona, Spain

    Sonia Servitja, Laia Garrigós, Joan Albanell & Ignasi Tusquets

  7. Programa Consolider, Instituto de Salud Carlos III/FEDER, Barcelona, Spain

    Sonia Servitja, Laia Garrigós, Joan Albanell & Ignasi Tusquets

  8. Internal Medicine Department, Parc de Salut Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain

    Adolfo Diez-Perez & Xavier Nogues

  9. Lifecourse Epidemiology Unit, MRC Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK

    Cyrus Cooper

Authors
  1. Daniel Prieto-Alhambra
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  2. Sonia Servitja
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  3. M. Kassim Javaid
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  4. Laia Garrigós
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  5. Nigel K. Arden
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  6. Cyrus Cooper
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  7. Joan Albanell
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  8. Ignasi Tusquets
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  9. Adolfo Diez-Perez
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  10. Xavier Nogues
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Correspondence to Xavier Nogues.

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Prieto-Alhambra, D., Servitja, S., Javaid, M.K. et al. Vitamin D threshold to prevent aromatase inhibitor-related bone loss: the B-ABLE prospective cohort study. Breast Cancer Res Treat 133, 1159–1167 (2012). https://doi.org/10.1007/s10549-012-2013-9

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