Osteoporosis was defined as BMD
Osteoporosis was defined as BMD 2.5 standard deviations or more below the reference range mean for young adults. Osteopaenia being those with a BMD between 1 and 2.5 standard deviations below the young adult mean . Lumbar spine (L2-L4) and femoral neck BMD was quantified with Lunar DPX-L (Lunar, Madison, WI, USA), GE-Lunar Prodigy (Prodigy; GE Lunar, Madison, WI, USA) or Norland Excell™ machines. Dual-energy X-ray absorptiometry (DXA) at baseline, 1, 2 and 3 years assessed using Norland machines were converted to Lunar equivalents using the Genant conversion equations . N-telopeptide (NTx) is a marker of bone resorption. Urine samples for urinary N-telopeptide (uNTx) were collected at baseline, and at 6 months after registration. Participants requiring alendronate were retested 6 months after commencing alendronate.
All patients were commenced on oral anastrozole 1mg daily, calcium (≥ 500mg per day) and Vitamin D (≥ 400 IU daily) supplements. No dose modifications were permitted for the duration of the study for those receiving either anastrozole or alendronate.
In accordance with the OAA, patients with a BMD T-Score below −2.5 S.D. at either the lumbar vertebra or femoral neck at any time-point, were commenced on alendronate 70mg oral weekly. Patients with a T-score between −2.0 S.D. and −2.5 S.D. commenced alendronate if the index of bone mineral turnover was elevated >20% at the 6-month time-point. If the BMD T-Score fell below −2.0 S.D. at either the lumbar vertebra or femoral neck at any time during the five-year treatment period, bone mineral turnover studies were instituted. If the bone mineral turnover studies indicated that sr9009 the biochemical marker (uNTx) was elevated more than 20% over baseline, then bisphosphonate therapy was instituted.
Different influences on lipid profiles have been observed in trials comparing aromatase inhibitors to tamoxifen . For safety reasons, a fasting lipid assessment (LDL, HDL, total cholesterol and triglycerides) was measured at baseline and repeated at the 6-month trial visit for all participants. Vitamin D level was measured at baseline.
Statistical analysis BMD was analysed using a repeated measures model that implicitly allowed for missing data and assessed dependent samples over time with the multiple comparison Tukeys test applied. The level of significance was set at p=0.05.
Discussion Based on the results of genes three-year analysis, alendronate effectively increases BMD in osteoporotic, postmenopausal women with early breast cancer who are receiving adjuvant therapy with anastrozole. This subgroup of women would have the greatest risk of bone loss and fracture. The benefit seen with bisphosphonate therapy was greater at the spine than at the hip but did significantly improve both spine and hip BMD (15.6%, p<0.01 and 5.6%, p<0.01 at 3 years respectively). Prior studies, such as Z-FAST , have mostly reported the impact of bisphosphonates on BMD in women with osteopaenia. Our findings are consistent with the results from the ARIBON trial that included 13 osteoporotic women who received anastrozole and ibandronate contributing to an increased BMD of 3.52% and 2.49% for the lumbar spine and hip at 2 years . Subsequent results of this study continue to show an increase in lumbar BMD (9.65%) and at the hip (2.72%) for the 9/13 patients in the osteoporotic group when assessed at their 5 year follow-up, demonstrating the ability to use AI therapy currently with a bisphosphonate in these women . Our study also confirms the safety of commencing aromatase inhibitors in this frequently excluded sub-group. BMD of the spine, but not at the hip, demonstrated a significant increase of 6.3%, p=0.02 at 3 years in the osteopaenic group receiving early intervention with alendronate. However, we did not demonstrate an improvement in BMD for the osteopaenic group receiving late intervention with alendronate. Patient numbers were small and larger benefit might be expected with longer follow \'up\' of these patients. These late intervention patients triggered the algorithm and started on alendronate at different time points (<18 months; 18–24 months; 24–36 months; >36 months). This results in a confounding proportion of patients within this group with ongoing BMD loss prior to starting bisphosphonate therapy.