br D microCT data Bone volume BV TV ranged

3D microCT data Bone volume (BV/TV) ranged from 10.8 to 13.5% consistent with the published literature [18]. Trabecular thickness (Tb.Th), trabecular lxr agonist (Tb.Sp), trabecular number (Tb.N) and bone surface per tissue area (BS/TV) values were also consistent with the range published in the literature in post-menopausal women [18]. 3D microCT data are located in Table 2. The accompanying figures for each biopsy are located in Fig. 1.
Discussion Despite the widespread use of bone-targeted agents in breast cancer patients, there is a relative paucity of data about the in vivo effect of these agents on bone homeostasis, bone quality, and microarchitecture in humans [1]. This is not withstanding that we are using increasingly potent agents at higher doses and increased frequencies, relative to their use in the treatment of osteoporosis. This is important as long-term bisphosphonate use confers prolonged suppression of bone remodeling sites which can have deleterious clinical effects [3,19–22]. Newer methods for assessing bone quality are under investigation, such as microindentation technique and high-resolution peripheral quantitative CT [23–25], but are regarded as exploratory. High resolution-peripheral quantitative CT appears to be better than DEXA at predicting fracture risk, but has not yet reached widespread clinical use [24–27]. Further, the use of biochemical turnover markers [8] are primarily used for monitoring treatment efficacy and compliance, and do not directly assess bone quality. Bone histomorphometry remains the gold standard in evaluating bone status prior to and following therapeutic interventions. However, this invasive procedure is not amenable to routine use. In cancer patients bone marrow biopsy is frequently used for pathological assessment and we explored the possibility to extend its use to bone histomorphometric parameters. We therefore assessed the feasibility of using 2mm core biopsies to obtain additional information on in vivo bone biology indices. The current study demonstrates that using a 2mm Jamshidi is feasible, practical and yields a sample sufficient to determine trabecular microarchitecture and bone turnover indices by both microCT and histomorphometry. The benefit of this technique is that it provides qualitative information on the in vivo effect of bone-targeted agents on bone quality.This technique may also provide a feasible means of assessing bone quality in cancer patients on therapies known to affect bone quality (e.g., tamoxifen, aromatase inhibitors). Previous studies have used BMD in this setting, but it has its limitations and is not able to assess bone quality [28–30]. The importance of assessing bone quality and balancing the potential risks against the benefits of bone toxic agents will be of paramount importance if such agents (e.g., exemestane) are used for primary prevention of breast cancer [23,31]. The findings of this prospective, pilot study are limited by the small sample size, but recruitment is currently under way to expand the study cohort. Another important limitation is that preclinical models have demonstrated that the effect of bisphosphonates on bone turnover is highly site specific [32]. The implications are that data from a single biopsy site (i.e. iliac crest) may not be representative of global bone quality [32,33]. There were, however, several findings that merit consideration. Patient #1 had metastatic cancer to soft tissues but no bone metastasis and was treated with aromatase inhibitors but not with bisphosphonates. Bone histomorphometry revealed active bone turnover as indicated in Table 3. In contrast patient #3 who had limited bone metastatic disease was treated with both aromatase inhibitors and bisphosphonates and had evidence of bone suppression with no active osteoclast detected. Patient #2 was of particular interest because of extensive bone metastasis by skeletal survey and its confirmation by the presence of metastatic tumor on histomorphometric sections (Fig. 2). Interestingly this patient had very active osteoclastic activitiy as indicated in Table 3 despite treatment with intravenous bisphosphonates for three years suggesting that bisphosphonates were unable to completely suppress turnover when tumor burden is high. Given our sample size, it is premature to generalize our findings but it provides a rationale to extend our study with a larger sample size to assess the reproducibility of our findings and whether or not a 2mm core will be able to replace the use of 7mm core biopsies.