AI-related BMD variation in actual practice conditions: A prospective cohort study.

The aim of the study was to evaluate the progression of bone mineral density (BMD) during 3 years of aromatase inhibitors (AI) therapy in actual practice conditions. This prospective, clinical cohort study of Barcelona-Aromatase induced Bone Loss in Early breast cancer (B-ABLE) assessed BMD changes during 3 years of AI treatment in women with breast cancer. Patients with osteoporosis (T score < -2.5 or T score ≤ -2.0) and a major risk factor and/or prevalent fragility fractures were treated with oral bisphosphonates (BPs). Of 685 women recruited, 179 (26.1%) received BP treatment. By the third year of AI therapy, this group exhibited increased BMD in the lumbar spine (LS; 2.59%) and femoral neck (FN; 2.50%), although the increase was significant only within the first year (LS: 1.99% and FN: 2.04%). Despite BP therapy, however, approximately 15% of these patients lost more than 3% of their baseline bone mass. At 3 years, patients without BP experienced BMD decreases in the LS (-3.10%) and FN (-2.79%). In this group, BMD changes occurred during the first (LS: -1.33% and FN: -1.25%), second (LS: -1.19% and FN: -0.82%), and third (LS: -0.57% and FN: -0.65%) years of AI treatment. Increased BMD (>3%) was observed in just 7.6% and 10.8% of these patients at the LS and FN, respectively. Our data confirm a clinically relevant bone loss associated with AI therapy amongst nonusers of preventative BPs. We further report on the importance of BMD monitoring as well as calcium and 25-hydroxy vitamin D supplementation in these patients.

Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance.

Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables.

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

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 D(3) (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/cm(2) [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.

Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer.

OBJECTIVE: Baseline bone health in postmenopausal women is poorly characterized in prospective series of early breast cancer (EBC) patients candidates to aromatase inhibitor (AI) therapy. Our objective is to comprehensively evaluate bone health in a prospective clinical cohort of patients recruited prior to adjuvant AI therapy, with the aim of establishing potential AI impact on bone loss and fractures. METHODS: From January 2006 to April 2010, we consecutively included 343 women with EBC who were about to start adjuvant AI therapy. Participants were assessed at baseline (before AI initiation) and at 3 months, with annual assessments thereafter. Bone mineral density (BMD), spine X-ray, bone metabolism (vitamin D [25(OH)D], bone turnover markers [BTM]), arthralgia and quality of life are measured. RESULTS: Mean age was 61.9 years; 197 (57.4%) had been previously treated with tamoxifen; 145 (42.3%) were taking exemestane, 187 (54.5%) letrozole, and 11 (3.2%) anastrozole. Analysis of baseline data shows only 59 women (17.7%) had normal BMD; 200 (60.1%) had osteopenia and 74 (22.2%) had osteoporosis; 39 women (11.4%) had a prevalent fracture, 293 (89.1%) had 25(OH)D insufficiency (<30 ng/ml), and 61 (18.5%) severe deficiency (<10 ng/ml). Low 25(OH)D concentrations were associated with lower BMD and 233 (67.9%) participants had some degree of arthralgia. CONCLUSIONS: Low bone mass, prevalent fractures and vitamin D insufficiency were highly prevalent among candidates to adjuvant AI for EBC. Therefore, it is crucial to assess BMD, prevalent fractures and 25(OH)D concentrations before starting AI therapy and during follow-up.