Association of Bone Metastasis With Early-Stage Breast Cancer in Women With and Without Precancer Osteoporosis According to Osteoporosis Therapy Status

JAMA Netw Open. 2019 Mar 1;2(3):e190429. doi: 10.1001/jamanetworkopen.2019.0429.


Importance: Deaths from cancer are attributed more to secondary than primary tumors, but the pathogenesis of organ-specific cancer metastasis has not been determined.

Objective: To investigate whether precancer osteoporosis and osteoporosis therapy are associated with alteration of bone metastasis patterns.

Design, setting, and participants: This nationwide retrospective cohort study was performed from January 1, 2002, to December 31, 2013, using 2 cohorts from the Taiwan National Health Insurance Research Database: a random sample of 1 million beneficiaries from the Longitudinal Health Insurance Database who were enrolled in 2005 (LHID2005) and a specific data set of all the patients with osteoporosis. Patients diagnosed with breast cancer and precancer osteoporosis from January 1, 2002, to December 31, 2011, were included in the study, and their records were examined through December 31, 2013. From LHID2005, we selected 9104 women with early-stage breast cancer, of whom 705 had precancer osteoporosis. We identified 29 183 patients from the cohort of patients with breast cancer and osteoporosis, 14 020 of whom had precancer osteoporosis. Data analysis was performed from December 31, 2016, to August 31, 2018.

Exposures: Precancer osteoporosis and osteoporosis therapy.

Main outcomes and measures: The risk of bone metastasis in patients with and without precancer osteoporosis and patients receiving and not receiving osteoporosis therapy as well as time to bone metastasis development.

Results: Among 9104 patients with breast cancer from the Longitudinal Health Insurance Database (mean [SD] age, 46.7 [14.0] years), precancer osteoporosis was not associated with a difference in risk of bone metastasis (adjusted hazard ratio [aHR], 0.87; 95% CI, 0.58-1.30; P = .49). Among 14 020 patients with precancer osteoporosis from the other cohort (mean [SD] age, 58.9 [11.6] years), osteoporosis therapy had no association with the risk of bone metastasis (bisphosphonates: aHR, 1.47; 95% CI, 1.00-2.17; P = .05; nonbisphosphonate drugs: aHR, 1.00; 95% CI, 0.72-1.39; P > .99). Compared with those without precancer osteoporosis (median time to bone metastasis development, 2.87 years; interquartile range [IQR], 1.34-4.86 years), among those with precancer osteoporosis, the median time to develop bone metastasis was shorter in those who did not receive treatment (1.74 years; IQR, 0.58-3.60 years; P < .001), whereas this time was the same for those who received treatment (bisphosphonates: 2.34 years; IQR, 1.23-3.13 years; nonbisphosphonate drugs: 2.08 years; IQR, 0.92-4.95 years).

Conclusions and relevance: Precancer osteoporosis was not associated with risk of bone metastasis, but untreated osteoporosis was associated with accelerated progression of bone metastasis when it occurred. Organ microenvironments interact with disseminated cancer mostly after the specific organ has been predetermined to be the designated location. Because recurrences and metastases are major obstacles to cancer treatments, determining which organs may be at risk for metastases may be crucial to treating the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms* / complications
  • Bone Neoplasms* / epidemiology
  • Bone Neoplasms* / secondary
  • Bone Neoplasms* / therapy
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Female
  • Humans
  • Osteoporosis* / complications
  • Osteoporosis* / drug therapy
  • Osteoporosis* / epidemiology
  • Retrospective Studies
  • Young Adult


  • Bone Density Conservation Agents