Cancer Treatment Today

Collagen Crosslinks are purported to be useful to assess bone turnover. Bone turnover markers are biochemical markers of either bone formation or bone resorption. Commercially available tests are available to assess some of these markers in urine and/or serum by high performance liquid chromatography (HPLC) or immunoassay. Assessment of bone turnover markers is proposed to supplement bone mineral density (BMD) measurement in the diagnosis of osteoporosis and to aid in treatment decisions. Bone turnover markers could also potentially be used to evaluate treatment effectiveness before changes in BMD can be observed.

A 2011 systematic review by Funck-Brentano et al 1 addressed the issue of whether early changes in serum biochemical bone turnover markers predict the efficacy of osteoporosis therapy8 Their review included 24 studies that presented correlations between bone turnover markers and the outcomes of fracture risk reduction or change in BMD. Five studies (including the Bauer study, previously described) reported on fracture risk, and 20 studies reported on BMD changes. The review authors discussed study findings qualitatively but did not pool study results. The evidence did not support a correlation between short-term changes in bone turnover markers and fracture risk reduction. In addition, few studies were available on this topic, leading to the conclusion that bone turnover markers “have shown limited value” as a technique to monitor osteoporosis therapy. An additional study on this topic was published by Baxter et al in 2013. 2 This was a retrospective review of data on 200 patients commencing treatment with bisphosphonates for osteoporosis or osteopenia requiring treatment. The investigators found statistically significant inverse correlation between change in urine NTx at 4 months and change in spine BMD at 18 months (Pearson product-moment correlation r=0.33, p<0.001). There was not a significant association between change in urine NTx and hip BMD.
The 2013 guideline from the National Osteoporosis Foundation states that biochemical markers of bone turnover can be used to predict the extent of fracture risk reduction when measured 3 to 6 months after starting FDA-approved osteoporosis treatments 3. ON the otehr hand, a subanalysis of the randomized Fracture Intervention Trial (n=6184) by Bauer et al found that pretreatment levels of the bone turnover marker PINP significantly predicted the antifracture efficacy of alendronate. 4

Relevance of this test to Zometa therapy in multiple myeloma patients must be questioned. To my knowledge, there had never been a study in this population, which is very distinct from osteoporosis.

Verzenio after Ibrance: 

The one paper by Wander et al  that looked at Verzenio after Ibrance concluded that more study is needed: “demonstrate that a substantial proportion of pts continue to derive clinical benefit with abemaciclib after prior CDK4/6i, highlighting the potential for its use following CDK4/6 blockade. A second subset had early progression, suggesting cross-resistance to CDK4/6i via common pathways. Future effort should be directed towards validating potential biomarkers to guide optimal utilization of continued CDK4/6 blockade in HR+/HER2- MBC.”.

Seth Andrew Wander et al,A multicenter analysis of abemaciclib after progression on palbociclib in patients (pts) with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC). ournal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 1057-1057.

1. Funck-Brentano T, Biver E, Chopin F, et al. Clinical utility of serum bone turnover markers in postmenopausal osteoporosis therapy monitoring: a systematic review. Semin Arthritis Rheum. Oct 2011;41(2):157-169.
2.Baxter I, Rogers A, Eastell R, et al. Evaluation of urinary N-telopeptide of type I collagen measurements in the management of osteoporosis in clinical practice. Osteoporos Int. Mar 2013;24(3):941-947.
3.National Osteoporosis Foundation. 2014 Clinician’s guide to prevention and treatment of osteoporosis. http://nof.org/files/nof/public/content/file/2610/upload/895.pdf. .
4. Burch J, Rice S, Yang H, et al. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Health Technol Assess. Feb 2014;18(11):1-180.