Role of Trabecular Bone Score in supporting the management of patients with cancer 

Background

The absolute number of cancer cases has increased over the last decade, likely due to factors such as population growth and aging. However, advances in cancer prevention, detection, and treatment have contributed to a decrease in the age-adjusted incidence and mortality rates of cancer over this same period¹.

The primary goal of cancer treatment is to effectively and rapidly target and treat the cancer. Recent advances in treatment have significantly increased survival after cancer².

While cancer treatments have become more advanced and efficacious, one complication of some cancer treatments is secondary osteoporosis.

Understanding osteoporosis

Osteoporosis is conceptually defined as a systemic skeletal disease characterized by low bone mass and deterioration of bone microarchitecture, leading to bone fragility and a consequential increase in fracture risk.

Secondary osteoporosis is associated with factors other than age and menopause, and affects both the density and quality of bone, leading to weakened skeletal strength. It is often asymptomatic until a fracture occurs, typically in the spine, hip, or wrist.

Risk factors for bone loss include aging, hormonal changes, specific medications, and medical conditions such as cancer.

Loss of bone mass and degradation of bone microarchitecture, can occur with certain cancer treatments associated with increased risk of secondary osteoporosis, including the use of aromatase inhibitors in breast cancer.

Osteoporosis is assessed using dual energy X-ray absorptiometry (DXA) and consideration of clinical risk factors, for example, by FRAX®.

Clinical relevance of Trabecular Bone Score

Trabecular Bone Score software is a validated index of bone microarchitecture, which is acquired at the same time as a bone mineral density (BMD) assessment during a DXA scan.

TBS identifies normal, degraded or partially degraded bone microarchitecture, in order to provide a more complete insight into bone health and fracture risk.

TBS, as an indicator of bone quality, predicts fracture independent of BMD and clinical risk factors. Further, TBS is affected in most causes of secondary osteoporosis³.

The addition of TBS to a bone health assessment, can also help identify patients at increased risk of fracture, who are non-osteoporotic by BMD alone³.

Cancer Treatment-Induced Bone Loss & Fracture Risk Cancer treatments, such as chemotherapy, hormonal therapy and glucocorticoids, can lead to significant bone loss. In particular, treatments prescribed for breast cancer in women and prostate cancer in men, are associated with high rates of bone loss⁴.

Aromatase inhibitors are first-line therapies for reducing the risk of cancer recurrence in postmenopausal women with hormone-receptor-positive breast cancer, by inhibiting the conversion of androgens to estrogen. Given this mechanism of action, these therapies accelerate bone turnover, increase bone resorption and increase fragility fracture risk⁵.

In a longitudinal study of postmenopausal women with breast cancer (mean age 59 y), aromatase inhibitor treatment for 3 years negatively affected both BMD and TBS⁶. The loss of TBS was more pronounced during the first year of treatment with a slowing thereafter⁷.

In women with early hormone-positive breast cancer and treated with aromatase-inhibitors, BMD and FRAX identified 13% of patients with elevated fracture risk. The addition of TBS alongside FRAX and BMD, increased this proportion to 20%⁷.

Androgen deprivation therapy is associated with bone loss in men with prostate cancer⁸.

Osteoporosis is twice as common in young adult cancer patients post-hematopoietic stem cell transplantation compared to those not receiving transplantation. The risk of fracture has also been reported to be 1.4 times higher post-transplant⁹.

The cumulative risk of fracture also increases with longer treatment durations¹⁰.

Assessment and Management of Bone Health in Cancer Patients

DXA® assessment is frequently recommended prior to and during cancer treatment. Repeated DXA® is then recommended every two years or as clinically indicated⁴.

Recommendations for the assessment and management of cancer treatment-induced bone loss are provided in guidelines including the American Society of Clinical Oncology Management of Osteoporosis in Survivors of Adult Cancers with Nonmetastatic Disease: Clinical Practice Guideline⁴, Canadian Bone Health and Bone-Targeted Therapies for Prostate Cancer guideline¹¹ and the European Society for Medical Oncology’s Bone Health in Cancer¹².

TBS alongside BMD and FRAX, identifies a higher proportion of patients with increased fracture risk^7,13.

Treatment can include bone-targeting agents, calcium and Vitamin D supplementation, and other appropriate interventions^14,15.

Denosumab, a RANK ligand inhibitor, may be particularly useful in patients with bone metastases or those receiving aromatase inhibitors¹⁶. Denosumab has shown to be effective for inducing increases in TBS and an accompanying reduction in risk of vertebral fractures in women treated with aromatase inhibitors¹⁶.

Summary

TBS, as a validated index of bone microarchitecture, provides a valuable complement to traditional BMD assessments in clinical practice and can be especially useful for patients receiving cancer treatments known to impact bone health, including aromatase inhibitors for breast cancer and androgen deprivation therapy for prostate cancer.

The use of TBS enhances the ability of healthcare providers to more accurately identify and manage the risk of osteoporosis in cancer patients, thereby contributing to the overall goal of enhancing patient care and outcomes.

References

1. Global Burden of Disease 2019 Cancer Collaboration. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. JAMA Oncol. 2022 Mar 1;8(3):420–44.

2. Bhatia R, Holtan S, Jurdi NE, Prizment A, Blaes A. Do Cancer and Cancer Treatments Accelerate Aging? Curr Oncol Rep. 2022;24(11):1401–12.

3. Shevroja E, Reginster JY, Lamy O, Al-Daghri N, Chandran M, Demoux-Baiada AL, et al. Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International Osteoporosis Foundation (IOF) under the auspices of WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Aging. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2023 Jul 1;

4. Shapiro CL, Van Poznak C, Lacchetti C, Kirshner J, Eastell R, Gagel R, et al. Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline. J Clin Oncol. 2019 Nov;37(31):2916–46.

5. Tseng OL, Spinelli JJ, Gotay CC, Ho WY, McBride ML, Dawes MG. Aromatase inhibitors are associated with a higher fracture risk than tamoxifen: a systematic review and meta-analysis. Ther Adv Musculoskelet Dis. 2018 Apr;10(4):71–90.

6. Catalano A, Gaudio A, Agostino RM, Morabito N, Bellone F, Lasco A. Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors. J Endocrinol Invest [Internet]. 2019 May 24 [cited 2019 Jun 18]; Available from: https://doi.org/10.1007/s40618-019-01063-0

7. Mariotti V, Page DB, Davydov O, Hans D, Hudis CA, Patil S, et al. Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score. J Bone Oncol. 2017 Jun 1;7:32–7.

8. Diamond TH, Higano CS, Smith MR, Guise TA, Singer FR. Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy. Cancer. 2004;100(5):892–9.

9. Lin JN, Chen HJ, Yang CH, Lai CH, Lin HH, Chang CS, et al. Risk of osteoporosis and pathologic fractures in cancer patients who underwent hematopoietic stem cell transplantation: a nationwide retrospective cohort study. Oncotarget. 2017 Mar 31;8(21):34811–9.

10. Kim DK, Lee HS, Park JY, Kim JW, Ahn HK, Ha JS, et al. Androgen-deprivation therapy and the risk of newly developed fractures in patients with prostate cancer: a nationwide cohort study in Korea. Sci Rep. 2021 May 12;11(1):10057.

11. Saylor PJ, Rumble RB, Tagawa S, Eastham JA, Finelli A, Reddy PS, et al. Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline. J Clin Oncol Off J Am Soc Clin Oncol. 2020 May 20;38(15):1736–43.

12. Coleman R, Hadji P, Body JJ, Santini D, Chow E, Terpos E, et al. Bone health in cancer: ESMO Clinical Practice Guidelines†. Ann Oncol. 2020 Dec 1;31(12):1650–63.

13. Siddiqui MF, Maalouf NM. Impact of Incorporating Trabecular Bone Score Into Fracture Risk Assessment and Recommendation for Use of Bone-Modifying Agents in Women With Breast Cancer. Clin Breast Cancer. 2022 Feb 1;22(2):e239–41.

14. Guise TA. Bone Loss and Fracture Risk Associated with Cancer Therapy. The Oncologist. 2006 Nov 1;11(10):1121–31.

15. Handforth C, D’Oronzo S, Coleman R, Brown J. Cancer Treatment and Bone Health. Calcif Tissue Int. 2018 Jan 20;1–14.

16. Antonini S, Pedersini R, Birtolo MF, Baruch NL, Carrone F, Jaafar S, et al. Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors. J Endocrinol Invest [Internet]. 2023 Aug 17 [cited 2023 Aug 22]; Available from: https://doi.org/10.1007/s40618-023-02174-5.