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Effect of physical activity on bone strength and body composition in breast cancer premenopausal women during endocrine therapy 4

IN C ER O V P A Y R M IG E H DI T C ® A

K. HOJAN 1, P. MILECKI 2, M. MOLIŃSKA-GLURA 3, A. ROSZAK 2, P. LESZCZYŃSKI

Background. Breast cancer endocrine therapy (ET) is one of the most basic therapeutic methods in oncology. Well-balanced physical activity exerts positive influence on bone strength (BS) and body composition (BC), which has been confirmed by the clinical research regarding osteoporosis, prevention and treatment alike. Accordingly, in the following study, an attempt was made to assess the selected parameters of young, premenopausal women’s clinical state under the influence of breast cancer ET, as well as to define the influence of physical activity on the studied parameters. Aim. The assessment of the influence of aerobic and resistance training (AT and RT) on BS and BC in premenopausal women during breast cancer ET. Design. This was a nonrandomized, prospective clinical study. Setting and population. The study was performed in 41 outpatients in the Greater Poland Cancer Centre. Methods. The examinations were made with the anthropometric and dual energy X-ray absorptiometry measurements. The examinations were conducted according to the schedule: at the baseline, II-after 6 months of ET, III-after 6 months of AT (in 12 months of ET), IV- after following 6 months AT and RT (18 months of ET). Results. After 6 months of the ET without physical activity the bone mineral density (BMD) in all regions and the hip structure parameters were lower in comparison to the baseline and there was a significant increase in fatty tissue. After 6 months of AT the BMD of all regions was lower than in 6 months ET. An introduction of RT caused the analyzed values of BS parameters to increase. Also a significant growth of lean body mass and free fat body mass was observed and so was an insignificant fall in fat. Conclusion. The breast cancer ET is related to the chang-

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EUR J PHYS REHABIL MED 2013;49:331-9

Corresponding author: K. Hojan MD, PhD, Department of Rehabilitation, The Greater Poland Cancer Center, 15 Garbary Street, 61-866 Poznan, Poland. E-mail: [email protected]

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1Depatment of Rehabilitation Greater Poland Cancer Centre, Poznan, Poland, 2Department of Electroradiology University of Medical Sciences, Poznan, Poland, 3Department of Computer Science and Statistics University of Medical Sciences, Poznan, Poland 4Department of Physiotherapy Rheumatology and Rehabilitation University of Medical Sciences, Poznan, Poland

es in BS and BC in premenopausal women. The introduction of AT caused a slowdown in negative changes in bones, and body fat was reduced. The introduction of RT reversed an adverse tendency for BS and sarcopenia. Clinical Rehabilitation Impact. The study results show that mixed type physical activity (AT and RT) during breast cancer ET could prevent negative changes, of this treatment, in body build in premenopausal women. Key words: Neoplasm - Exercises - Hormones - Osteoporosis - Obesity.

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he decrease of sexual hormones level is the cause of menopausal symptoms, osteoporosis, and adverse metabolic changes.1, 2 The changes caused by drugs blocking ovaries function in women with breast cancer seem to be similar to the postmenopausal ones. Estrogen deficiency leads to the rise in the number of osteoclasts increasing their longevity.2, 3 In postmenopausal period an increase in body mass is connected with unfavourable redistribution of fatty tissue with a rise in the amount of visceral fat, as well as a fall in free fat body mass (FFBM).2, 4, 5 So far, publications on the impact of changes associated

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EFFECT OF PHYSICAL ACTIVITY ON BONE STRENGTH AND BODY COMPOSITION IN BREAST CANCER PREMENOPAUSAL WOMEN

Cancer Centre in Poznan, on the basis of criteria (Table I). All study procedures were reviewed and approved by the Bioethics Committee at the University of Medical Sciences in Poznan, and all participants signed informed consent. Study scheme The study was a nonrandomized, prospective clinical study. The following examination schedule was used: —— the baseline evaluation – before the ET; —— control examination – after 6 months of ET; —— an examination after 6 months of AT - after 12 months of ET; —— a final examination after 6 months of mixed physical activity (AT and RT) - after 18 months of ET. The examinations were conducted according to the following scheme: a subjective examination, objective examination, anthropometrical measurements, and dual-energy X-ray absorptiometry (DXA).


with endocrine therapy (ET) in breast cancer have shown their negative influence on bone strength due to a decrease in BMD,2, 6, 7 and on body composition (increased adiposity and sarcopenia).2, 4, 8 It was also confirmed that regular exercise has a positive impact on bone mineralization improvement and stimulation of osteogenesis.9 The effects of physical exercise on change in body composition were also described in postmenopausal women.8, 10 Existing research studying the relative importance of lean and fat tissue in stimulating osteogenesis has established no consensus. Although several studies suggest an important or primary role of fat in determining bone mass and density,11-15 perhaps that role is the most pronounced in postmenopausal women.3 However, others have indicated that lean mass is dominant in women.15-17 It seems that physical exercise may also cause changes in bone strength and body composition in premenopausal women during ET for breast cancer. We had hypothesized that aerobic (AT) and resistance training (RT) would be associated with favorable changes in bone strength and body composition in this group patients with breast cancer. So, we conducted the study aimed to investigate the influence of physical activity on bone strength and body composition in premenopausal women with breast cancer during ET. Materials and methods Study participants

Forty one women receiving breast cancer treatment were selected for the study, conducted from September 2007 to June 2010 in The Greater Poland

Subjective examination

Additional factors which may influence bone density were considered and were excluded from the medical history of the subject study such as smoking for the last 5 years, alcohol abuse, taking glucocorticoids and other drugs affecting calcium (Ca)-economy, restrictive diets, non traumatic bone fractures incidences in close family. Moderate physical activity contraindications were also taken into consideration, such as heart failures with blood circulation failures above II NYHA, heart rhythm defects. Daily Ca intake was also assessed by the Ca intake ques-

Table I.—Study criteria.

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HOJAN

Criteria for inclusion in the study

Criteria for exclusion from the study

–– 18 to 50 years of age –– Female sex –– Regular menstruation till the introduction of ET –– Histopatologically confirmed breast tumor –– Planned hormonal treatment and its continuation for min. 18 months (goserelin 3.6 mg every 28 days and tamoxifen 20 mg every day) –– Lack of distant metastases –– Good general condition (ECOG 0-1) –– In the medical history the lack of endocrinological, rheumatic, cardiac diseases resulting in circulation failure (above II NYHA). absorption disorders and other tumors –– The exclusion of the calcium-phosphorus management affecting drugs especially steroids, vitamin D, calcium supplements, bisphosphonates

–– Not fulfilling the criteria for inclusion –– A patient’s resignation from the study before an 18 month period –– The introduction of chemotherapy –– Distant metastases and/or the disease progression resulting in radiotherapy –– A patient’s death

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June 2013

tionnaire ADOS-Ca.18 All participants completed a 120-item validated food frequency questionnaire at baseline and 6, 12, 18 months. Physical examination and anthropometrical measurements

DXA measures

The DXA measurements were taken with the Lunar Prodigy Advance device (GE, Madison, WI, USA) with enCORE software (GE Healthcare V. 10.50.086). All DXA scans were completed for each participant at baseline and 6, 12 and 18 months. The following measurements were taken: 1/ an examination of the total hip (TH) BMD (g/cm2); 2/ an examination of the spine with a BMD assessment in the lumbar region L1-L4; 3/ total body (TB) examination with BMD assessment. The Hip Strength Analysis (HSA) methodology uses engineering principles to extract data on the

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HOJAN

geometry of the proximal femur from DXA images (see: pp. 19-21). The HSA was also made on the basis of bone cross sectional area (CSA) (mm2) surface area of bone in the cross-section excluding soft tissue voids equivalent to an estimate of bone mineral content (g) and cross-sectional moment of inertia (CSMI) (mm4) were measured directly from mineral mass distributions using algorithms (see: p. 19). In the Hip Axis Length (HAL) (mm) the distance between the edge of the trochanter and the inner table of the pelvis was measured. The HAL has been shown in previous studies to be predictive of hip fracture independent of age and BMD hip.25 Femur strength index (FSI) was calculated as the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter.20 Of the body composition assessment the following were specified: the amount of free fatty body mass (FFBM) (g), lean body mass (LBM) (g), fat body mass (FBM) (g), and the percentage of total body fat (%TBF), the percentage of android fat (%AF), the percentage of gynoid fat (%GF).


At the baseline and during the study, apart from the general medical examination, the following laboratory examinations of hormone levels were performed: FSH, LH, E2, PG before ET and 6 months of the treatment. The anthropometrical measures: height, body mass, and waist and hip circumference were measured at baseline and 6, 12, 18 months. Height was measured using a stadiometer, rounding up to 0.5 centimeters. Body was weighted on digital scale (accuracy of ±10 g) in the morning after defecation, prior to a meal and physical activity. The waist circumference measure was taken with a tape, which was placed horizontally and parallel to the base so as to run across the deepest area of the body profile. The measure was taken twice with a patient holding her breath. If the two measurements differed from one another over 0.4 cm, then two more measurements were taken, and the results were used to calculate the arithmetic average. The hip circumference was taken also with a tape that was placed horizontally and parallel to the base so as to run across the most rear points. The one-off measurement was taken with a 150 cm tape on both limbs accurate to 0.1 cm. BMI and WHR (Waist to Hip Ratio) were calculated by means of the formulae: BMI[kg/m2] = body mass[kg]/(height)2[m2] and WHR= (waist circumference)[m]/(hip circumference)[m].

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Exercise programme

Aerobic

training

Between 6 and 12 month of ET the women exercised daily. The 40-45-minute exercises included brisk walk, outside or treadmill running, cycling. The workout consisted of a 2 minute warm-up, 40 minutes of one of the activities, and a 3-minute relaxation. The physical activity was moderate with the maximal heart rate of 65-75% of the maximum (220-age). In the course of the study some breaks from the exercises were allowed (maximally 3 days/ month). The training process was verified through patients’ physical activity notebooks and once-aweek by the person conducting the study.

Aerobic

and resistance training

Between 12 and 18 month of the study the patients took resistance exercises 3 times a week for about 40-45 minutes. All the exercises were performed with one or more physiotherapists assisting. The sessions were conducted with 1 to 2 sets of 6 to 8 isometric exercises (trunk muscles), 3 sets of upper body exercises with 10-15 repetitions and


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through the t-test for connected variables. The dependance between the results of the anthropometric measures and body composition and those of bone strength was attained through Pearson’s correlation rate. The results with P