# Exercise as it relates to Disease/Resistance training effects on bone turnover in postmenopausal breast cancer survivors

Source Article: Waltman, N.L., Twiss, J.J., Ott, C.D. et al. The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial. Osteoporos Int 21, 1361–1369 (2010). https://doi.org/10.1007/s00198-009-1083-y

## Background to the Research

In 2009 alone, roughly 193,000 United States women were diagnosed with breast cancer, with approximately 75% of these women predicted to be long-term survivors. Breast cancer survivors often experience early onset menopause due to chemotherapy. Menopause causes estrogen production to plummet resulting in reduced osteoblast and bone remodeling activity. Survivors of breast cancer therefore have decreased bone mineral density often leading to osteopenia and osteoporosis which significantly reduces quality and length of life.
Research has conclusively shown the effectiveness of medications such as calcium, vitamin D, and bisphosphonates in maintaining and improving bone mineral density. This paper investigates the use of strength training as an additional intervention to prevent decrease in bone mineral density. Previous findings on the impact of strength training on bone mineral density have been inconsistent. This paper's research is important as it seeks to provide clarity on whether strength training with medications has a positive effect on bone mineral density.

## Where the Research is From

Participants of this study are located in the United States with the authors being located at the University of Nebraska Medical Centre. This is important to note as a key contributor to reduction in bone mineral density is high sedentary behaviour, an issue that significantly affects the American population
All the authors in this study have experience in this field with lead author Nancy Waltman in particular having extensive experience and qualifications. She has been involved in research in cancer since 1990 and for the nine years leading up to the study, published eight articles exclusively focusing on bone health in breast cancer survivors. The study was federally-funded by the United States government, however, this should not affect findings due to the majority of cancer clinics being privately owned.

## Type of Research

The research undertaken in this study was a randomised control trial. This is a research method where participants are randomly allocated into either a control or intervention group. A randomised control trial is considered the gold standard of research as the comparison groups allow a cause and effect relationship to be established if there is indeed one. In this study the control group received only medications (risedronate, calcium, and vitamin D) to maintain bone mineral density whilst the intervention group received the medications and also completed strength training.
Randomised control trials like all research types can still be flawed. Researchers in this study could have strengthened the study design by blinding the assessors to the participant groups to help remove any bias. The design is also flawed as it only measures physical activity conducted in formal sessions. Bone mineral density could be improving due to other sources of physical activity in either group such as having to walk more regularly to attend strength training sessions or engaging in casual physical activity with friends. To strengthen future research a greater control of physical activity levels in both groups needs to be considered.

## What the Research Involved

A total of 223 subjects participate in the study; 113 in the medication group and 110 in the medication plus strength training group. Participants were recruited through media ads, support group meetings, and clinician offices. The study took place over 24 months to allow for the effects of a bone turnover cycle to be measured. Medications in both groups were delivered to subjects monthly in medication calendar cards. The medication plus exercise group undertook two sessions of strength training per week. The first nine months involved light weight training from home with the remainder of the study being undertaken in local fitness centres. Participants had fortnightly visits from exercise professionals to help adherence and safety whilst exercising. Bone mineral density was reported at baseline, 12 and 24 months in multiple locations using Dual Energy X-ray Absorptiometry (DEXA). Bone resorption and formation were assessed using alkaline phosphatase serum assay.
Limitations
The study had two key limitations. Due to the expensive nature of cancer treatment many breast cancer survivors in America are Caucasian including participants in this study. This means findings cannot be applied to minority female populations. The strength training group had an adherence rate of 69.4% which is low, likely due to the length of the study. To combat this the researchers used per protocol analysis, excluding low adherence participants from the data but this likely induces a positive bias favouring the effect of strength training.

## Results of the Research

Participants in the medication only group showed significant mean increases from baseline to 24 months in bone mineral density at the total hip and L1-L4 spine. Bone mineral density results at the femoral neck and total radius were not significant. Participants in the exercise group had additional increases in bone mineral density of +0.29% at the femoral neck, +0.34% at the total hip, +0.23% at the spine and +0.30 at the total radius. Whilst bone mineral density was higher in the exercise group the results were not significant.
Researcher Interpretation
The researcher's interpretation of the results are consistent and well thought out. The researchers acknowledge the improvement in bone mineral density across both groups noting the exercise group did see greater improvements, however they also acknowledge that findings were not significant. The researchers argue maintenance of bone mineral density alone, let alone increase, may be a satisfactory outcome of treatment regardless. The study suggests more research is required in strength training (specifically a larger amount of strength training per week) and adherence to exercise is required to form stronger conclusions.

## Conclusions Taken from the Research

This study suggests a link between strength training and improvement in bone mineral density in breast cancer survivors. Whilst the findings are not significant and therefore a cause and effect cannot be established, practical findings can still be drawn from the benefits of strength training and bone mineral density specific medications . The findings of this study are aligned with the other studies/results in this research area. Unfortunately the primary purpose of this study was to find consistent evidence on the effects of strength training in breast cancer survivors and the study failed to do this. It largely replicated what previous study methodology had been and relied on a larger number of participants to provide more conclusive evidence. Future research needs to look at different methodologies such as a greater amount of strength training with higher adherence.

## Practical advice

* Previous studies , including this one, show the conclusive positive effect of regular consumption of calcium, vitamin D, and bisphosphonates for breast cancer survivors in improving their bone mineral density. Medications and specific doses should only be prescribed by a doctor.
* To help maintain bone mineral density and increase muscular strength, breast cancer survivors should undertake strength training twice a week for 40 - 45 minutes.
* Breast cancer survivors should seek guidance from an exercise professional such as a physiotherapist or exercise physiologist to provide information on exercise selection, load and progression of their strength training.

## Further information/resources

As this critique is published in Australia, resources for Australians affected by cancer are provided.
Cancer Support and Physical Activity in Australia
* Breast Cancer Support Services Australia
* Cancer Australia
* Physical activity and exercise guidelines for all Australians.
Further Research
* Aerobic Exercise and Lumbar Spine Bone Mineral Density in Postmenopausal Women: A Meta-Analysis
* Dose-response effects of exercise on bone mineral density and content in post-menopausal women
* The effect of exercise on body composition and bone mineral density in breast cancer survivors taking aromatase inhibitors

## References

* 1 2 3 4 5 6 7 8 9 Waltman, N.L., Twiss, J.J., Ott, C.D. et al. The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial. Osteoporos Int 21, 1361–1369 (2010).
* 1 2 3 Winters-Stone, K.M., Dobek, J., Nail, L. et al. Strength training stops bone loss and builds muscle in postmenopausal breast cancer survivors: a randomized, controlled trial. Breast Cancer Res Treat 127, 447–456 (2011).
* 1 2 van Hellemond, I.E.G., Smorenburg, C.H., Peer, P.G.M. et al. Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial. Breast Cancer Res Treat 180, 675–685 (2020).
* ↑ Asikainen TM, Kukkonen-Harjula K, Miilunpalo S. Exercise for health for early postmenopausal women. Sports medicine. 2004 Sep;34(11):753-78.
* 1 2 Bergström I, Landgren BM, Brinck J, Freyschuss B. Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density. Osteoporosis International. 2008 Feb;19(2):177-83.
* 1 2 Uusi-Rasi K, Kannus P, Cheng S, Sievänen H, Pasanen M, Heinonen A, Nenonen A, Halleen J, Fuerst T, Genant H, Vuori I. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone. 2003 Jul 1;33(1):132-43.
* ↑ Silveira EA, Mendonça CR, Delpino FM, Souza GV, de Souza Rosa LP, de Oliveira C, Noll M. Sedentary behavior, physical inactivity, abdominal obesity and obesity in adults and older adults: A systematic review and meta-analysis. Clinical Nutrition ESPEN. 2022 Jun 14.
* 1 2 College of Nursing. Nancy Waltman, PhD, RN, APRN-NP [Internet]. Nebraska: University of Nebraska Medical Centre; 2022 July [cited 28 Aug 2022]. Available from: https://www.unmc.edu/nursing/faculty/profiles/nwaltman/index.html
* ↑ Lara Jr PN, Higdon R, Lim N, Kwan K, Tanaka M, Lau DH, Wun T, Welborn J, Meyers FJ, Christensen S, O’Donnell R. Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment. Journal of clinical oncology. 2001 Mar 15;19(6):1728-33.
* 1 2 3 Brocklehurst P, Hoare Z. How to design a randomised controlled trial. British dental journal. 2017 May;222(9):721-6.