Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Methods
2.1. Registration
2.2. Search Strategy
2.3. Selection Criteria
- (P) Participants: adult women (18 years and older) with non-metastatic BC.
- Intervention: any rehabilitation treatment administered before, during, or after chemotherapy and/or radiotherapy treatments.
- (C) Comparator: any comparator including pharmacological, non-pharmacological, or no treatment.
- (O) Outcome: primary outcomes were bone metabolic biomarkers. Secondary outcomes were other bone health outcomes, including bone mineral density or trabecular bone score.
2.4. Study Screening and Eligibility Assessment
2.5. Data Extraction and Synthesis
2.6. Meta-Analysis
2.7. Quality Assessment and Risk of Bias
3. Results
3.1. Study Characteristics
3.2. Participants
3.3. Control Groups
3.4. Rehabilitation Therapy Interventions
3.5. Primary Outcome—Bone Biomarkers Modifications
- Collagen type 1 cross-linked N-telopeptide (NTX) was assessed in four studies [33,35,36,38], but significant changes were reported only in one study [38]. In particular, Waltman et al. [38] reported significant changes (p < 0.05) in both the intervention group (RET + risedronate, calcium, and Vitamin D) and the control group (risedronate, calcium, and vitamin D).
- Osteocalcin was assessed in five papers [32,33,37,39,40]; out of these, two studies [32,33] reported a significant increase (both p < 0.05) in the intervention group after CET, while Winters-Stone et al., 2011, [39] reported a significative inter-group difference after RET combined with IET (p = 0.01). Lastly, Tabatabai et al. [37] reported a significant decrease in both intervention (CET) and control groups.
- Bone-specific alkaline phosphatase (BSAP) was assessed in four papers [33,35,36,38]; among these studies, Dieli-Conwright et al. [33] reported a significant increase in serum concentration in the CET intervention group compared to intervention; concurrently, Waltman et al. [38] reported a reduction in both the intervention group (RET + risedronate, calcium, and Vitamin D) and control group (risedronate, calcium, and Vitamin D). The remaining studies did not report a significant modification of BSAP values (p > 0.05).
- Receptor activator of nuclear factor (RANK) was assessed by Dieli-Conwright et al. [33], but the study did not report significant changes (p > 0.05).
- Receptor activator of nuclear factor ligand (RANKL) was assessed by Dieli-Conwright et al. [33], without reporting significant changes (p > 0.05).
3.6. Secondary Outcomes—Bone Mineral Density
- Lumbar spine BMD was assessed in seven studies [32,33,34,37,38,39,40]; more in-detail, Winters-Stone et al., 2011, [39] underlined significant changes (p < 0.01) in the intergroup analysis after RET combined with IET intervention after 12 months. Similarly, Waltman et al. [38] reported a percentage mean difference significant both in the intervention group (RET + risedronate, calcium, and vitamin D) and the control group (risedronate, calcium, and vitamin D) (both p < 0.05). Interestingly, Tabatabai et al. [37] reported a significant mean decrease in the control group, which received only a monthly health newsletter (p = 0.03).
- Radius (33% length) BMD was assessed by Waltman et al. [38], without reporting significant changes.
- Total radius BMD was assessed by Waltman et al. [38], with no significant changes after the intervention.
3.7. Meta-Analysis
3.8. Quality Assessment and Risk of Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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((“breast neoplasms” [MeSH Terms] OR (“breast” [All Fields] AND “neoplasms” [All Fields]) OR “breast neoplasms” [All Fields] OR (“breast” [All Fields] AND “cancer” [All Fields]) OR “breast cancer” [All Fields] OR “breast tumor” [MeSH Terms] OR (“breast” [All Fields] AND “tumor” [All Fields]) OR “breast tumor” [All Fields])) AND ((“rehabilitant” [All Fields] OR “rehabilitants” [All Fields] OR “rehabilitate” [All Fields] OR “rehabilitated” [All Fields] OR “rehabilitates” [All Fields] OR “rehabilitating” [All Fields] OR “rehabilitation” [MeSH Terms] OR “rehabilitation” [All Fields] OR “rehabilitations” [All Fields] OR “rehabilitative” [All Fields] OR “rehabilitation” [MeSH Subheading] OR “rehabilitation s” [All Fields] OR “rehabilitational” [All Fields] OR “rehabilitator” [All Fields] OR “rehabilitators” [All Fields] OR “exercise” [MeSH Terms] OR “exercise” [All Fields] OR (“physical” [All Fields] AND “exercise” [All Fields]) OR “physical exercise” [All Fields] OR “training” [All Fields] OR “train” [All Fields] OR “train s” [All Fields] OR “trained” [All Fields] OR “training s” [All Fields] OR “trainings” [All Fields] OR “trains” [All Fields])) AND ((“bone and bones” [MeSH Terms] OR (“bone” [All Fields] AND “bones” [All Fields]) OR “bone and bones” [All Fields] OR “bone” [All Fields]) AND (“biomarker s” [All Fields] OR “biomarkers” [MeSH Terms] OR “biomarkers” [All Fields] OR “biomarker” [All Fields]) OR (“bone remodeling” [MeSH Terms] OR (“bone” [All Fields] AND “remodeling” [All Fields]) OR “bone remodeling” [All Fields] OR (“bone” [All Fields] AND “turnover” [All Fields]) OR “bone turnover” [All Fields] OR “osteogenesis” [MeSH Terms] OR “osteogenesis” [All Fields] OR (“bone” [All Fields] AND “formation” [All Fields]) OR “bone formation” [All Fields] OR “bone resorption” [MeSH Terms] OR (“bone” [All Fields] AND “resorption” [All Fields]) OR “bone resorption” [All Fields])) | |
Scopus: | |
TITLE-ABS-KEY (((((((breast AND neoplasms) OR (breast AND cancer) OR (breast AND tumor)) AND ((rehabilitation) OR (rehabilitation AND therapy) OR (exercise) OR (physical AND exercise)) AND ((bone AND (biomarker OR biomarkers)) OR (bone AND remodelling) OR (bone AND turnover))))))) | |
Web of Science: | |
(((((breast neoplasms) OR (breast cancer) OR (breast tumor)) AND ((rehabilitation) OR (rehabilitation therapy) OR (exercise) OR (physical exercise)) AND ((bone biomarker) OR (bone biomarkers) OR (bone remodelling) OR (bone turnover))))) | |
Cochrane: | |
ID | Search |
#1 | MeSH descriptor: [breast neoplasms] explode all trees |
#2 | MeSH descriptor: [breast cancer] explode all trees |
#3 | MeSH descriptor: [breast tumor] explode all trees |
#4 | MeSH descriptor: [rehabilitation] explode all trees |
#5 | MeSH descriptor: [rehabilitation therapy] explode all trees |
#6 | MeSH descriptor: [exercise] explode all trees |
#7 | MeSH descriptor: [physical exercise] explode all trees |
#8 | MeSH descriptor: [bone biomarker] explode all trees |
#9 | MeSH descriptor: [bone biomarkers] explode all trees |
#10 | MeSH descriptor: [bone remodelling] explode all trees |
#11 | MeSH descriptor: [bone turnover] explode all trees |
#12 | (#1 OR #2 OR #3) AND (#4 OR #5 OR #6 OR #7) AND (#8 OR #10 OR #11) |
PEDro: | |
breast cancer, exercise, bone * |
Authors Journal Year | Participants | Cancer Treatments | ||||||
---|---|---|---|---|---|---|---|---|
Sample Size | Age (Years) | BMI (kg/m2) | Cancer Characteristics | Breast Surgery | Chemotherapy | Radiation Therapy | Hormonal Therapy | |
Baker et al. Integr. Cancer Ther. 2018 [31] | N = 31 IG: 14 CG: 17 | N = 61.6 ± 8.3 IG: 61.6 ± 9.2 CG: 61.6 ± 7.8 | N = 28.8 ± 4.7 IG: 28.4 ± 3.9 CG: 29.1 ± 5.3 | Non-metastatic breast cancer | NR | NR | NR | 100% |
De Paulo et al. Exp. Gerontol. 2018 [32] | N = 36 IG: 18 CG: 18 | N = NR IG: 63.2 ± 7.1 CG: 66.6 ± 9.6 | N = NR IG: 28.9 ± 5.2 CG: 31.5 ± 6.3 | Stage I IG: 50% CG: 58.8% Stage II IG: 33.3% CG: 23.6% Stage IIIA IG: 17.6% CG: 17.6% | Partial Mastectomy IG: 47.4% CG: 58.8% Total Mastectomy IG: 52.6% CG: 41.2% | NR | NR | 100% |
Dieli-Conwright et al. Breast Cancer Res. 2018 [33] | N = 100 IG: 50 CG: 50 | N = 53.5 ± 10.4 IG: NR CG: NR | N = 33.5 ± 5.5 IG: NR CG: NR | Stage I: 40% Stage II: 38% | NR | Chemotherapy and radiotherapy (76%) | Chemotherapy and radiotherapy (76%) | NR |
Kim et al. Cancer Nurs. 2016 [34] | N = 43 IG: 23 CG: 20 | N = NR IG: 55.7 ± 5.3 CG: 56.3 ± 6.7 | N = NR IG: 23.3 ± 4.3 CG: 23.4 ± 2.5 | Stage 0-I: IG: 7 (31.8%) CG: 12 (60.0) Stage II-III: IG: 15 (68.2) CG: 8 (40.0) | Mastectomy: IG: 12 (52.2%) CG: 14 (20.0%) Breast-conserving surgery: IG: 11 (47.8%) CG: 16 (80.0%) | IG: 18 (78.3%) CG: 15 (75.0%) | IG: 14 (60.9%) CG: 16 (80.0%) | Selective estrogen receptor modulator IG: 13 (56.6%) CG: 9 (45%) Aromatase inhibitor IG: 5 (21.7%) CG: 8 (40.0%) |
Peppone et al. Clin Breast Cancer 2010 [36] | N = 16 IG: 7 CG: 9 | N = NR IG: 53.8 CG: 52.6 | N = NR IG: 25.8 CG: 24.2 | Breast Cancer Stage 0-IIIB | Mastectomy IG: 57% CG: 33.3% Lumpectomy IG: 43% CG: 66.7% | NR | NR | IG: 42.9% CG: 66.7% |
Peppone et al. Support. Care Cancer 2018 [35] | N = 41 IG1 (exercise + supplementation): 10 IG2 (exercise): 10 IG3 (supplementation): 10 CG: 11 | N = 53.5 ± 7.8 IG1: ≤48 = 18.2% 49–57 = 54.5% ≥58 = 27.3% IG2: ≤48 = 10.0% 49–57 = 40.0% ≥58 = 50.0% IG3: ≤48 = 50.0% 49–57 = 20.0% ≥58 = 30.0% CG: ≤48 = 60.0% 49–57 = 20.0% ≥58 = 20.0% | N = NR IG1: 31.3 IG2: 32.4 IG3: 28.1 CG: 28.4 p = 0.29 | Stage 0-I IG1: 63.6% IG2: 20% IG3: 50% CG: 30% Stage II IG1: 27.3% IG2: 60% IG3: 40% CG: 40% Stage III IG1: 9.1% IG2: 20% IG3: 10% CG: 30% | NR | IG1: 54.5% IG2: 70% IG3: 70% CG: 70% | IG1: 100% IG2: 100% IG3: 100% CG: 100% | Tamoxifen IG1: 36.4% IG2: 44.4% IG3: 60% CG: 70% Aromatase inhibitor IG1: 63.6% IG2: 55.6% IG3: 40% CG: 30% |
Tabatabai et al. J. Clin. Endocrinol. Metab. 2016 [37] | N = 206 IG: 103 CG: 103 | N = NR IG: 46.0 ± 5.7 CG: 45.2 ± 5.9 | N = NR IG: 26.2 ± 6.0 CG: 25.7 ± 6.7 | Non-metastatic Breast Cancer | NR | 100% | NR | Tamoxifen IG: 49% CG: 72% |
Waltman et al. Osteoporos Int. 2010 [38] | N = 223 IG: 110 CG: 113 | ≤60 years IG: 55 CG: 61 >60 years IG: 45 CG: 39 | ≤25 IG: 42 CG: 34 >25 IG: 58 CG: 66 | Stage I–II breast cancer | NR | NR | NR | NR |
Winters-Stone et al. Breast Cancer Res Treat. 2011 [39] | N = 106 IG: 52 CG: 54 | N = NR IG: 62.3 ± 6.7 CG: 62.2 ± 6.7 | N = NR IG: 29.5 ± 5.8 CG: 29.5 ± 5.6 | Stage 0–IIIA breast cancer Stage 0 IG: 7.7% CG: 3.7% Stage I IG: 38.5% CG: 40.7% Stage II IG: 48.1% CG: 35.2% Stage IIIa IG: 1.9% CG: 9.3% | NR | IG: 61.5% CG: 59.3% | IG: 92.3% CG: 83.3% | IG: 59.6% CG: 53.7% |
Winters-Stone et al. Osteoporos Int. 2013 [40] | N = 71 IG: 35 CG: 36 | N = NR IG: 46.5 ± 5 CG: 46.4 ± 4.9 | N = NR IG: 27 ± 5.4 CG: 25.8 ± 4.6 | Stage I IG: 22.9% CG: 33.3% Stage II IG: 65.7% CG: 50% Stage III IG: 11.4% CG: 16.7% | NR | NR | IG: 62.9% CG: 61.1% | Aromatase inhibitors IG: 40% CG: 30.6% SERM IG: 37.1% CG: 44.4% |
Authors Journal Year | Intervention | Comparator | |||||||
---|---|---|---|---|---|---|---|---|---|
Type of Activity | Exercise Modality | Protocol Duration | Frequency | Volume (Session) | Intensity | Supervision or Home-Based | Timing | ||
Baker et al. Integr. Cancer Ther. 2018 [31] | WBV | WBV | 12 weeks | Three sessions/wk | 20 min | Low-frequency, low-magnitude vibration (30 Hz, 0.1 mm, 0.3 g) | Supervised | After chemotherapy and/or radiotherapy | Usual care |
De Paulo et al. Exp. Gerontol. 2018 [32] | CET |
| 36 weeks | Three sessions/wk | CET: 100 min (5 min warm-up, 55 min of RET, 30 min of AET, 10 min cooldown) | NR | Supervised | After chemotherapy and/or radiotherapy | Type of activity: low intensity stretching and relaxation Exercise modality: stretching and relaxation exercises Protocol duration: 36 weeks Frequency: Two sessions/wk Volume (session): 45 min per session Intensity: low intensity Supervised After chemotherapy and/or radiotherapy |
Dieli-Conwright et al. Breast Cancer Res. 2018 [33] | CET |
| 16 weeks | Three sessions/wk | 5 min warm-up; Days one and three: approximately 80 min of CET; Day two: AET progressively increased from 30 min up to 50 min; 5-min cool down at 40–50% estimated VO2 max | 80% of estimated 1-RM for lower body exercises and 60% estimated 1-RM for upper body, keeping target HR in AET at 60–80% of maximum, increased every 4 weeks | Supervised | After chemotherapy and/or radiotherapy | Usual care |
Kim et al. Cancer Nurs. 2016 [34] | CET |
| 6 months | AET: three nonconsecutive days; RET: two to three sessions/wk | AET: minimum 150 min/wk; RET: Two sets of 8–10 repetition | AET: 11 to 13 perceived exertions on a six to 20 point scale; RT: low to moderate intensity | Home-based + Telephone counseling | After chemotherapy and/or radiotherapy + Supplementation with 500 mg calcium and 1000 IU vitamin D | Supplementation with 500 mg calcium and 1000 IU vitamin D |
Peppone et al. Clin Breast Cancer 2010 [36] | thai chi chuan (TCC) exercises | Warm up, stretches, Chi Kung; TCC sessions consisting of a 15-move short form sequence of Yang-style of TCC; cool down with regulatory breathing, imagery, and meditation | 12 weeks | Three sessions/wk | NR | 10 min warm up; 40 min TCC sessions; 10 min cool down | Supervised | After chemotherapy and/or radiotherapy | Usual care + Behavioral coping strategies, cohort support and group unity. Patients instructed not to change their pattern of physical activity in any manner for the duration of the intervention |
Peppone et al. Support. Care Cancer 2018 [35] | CET |
| 12 weeks | RET: Three times per week with at least one rest day between the sessions; AET: Seven days/wk | RET: starting with an individually determined number of sets (7–10 repetitions) up to three sets for each exercise; AET: walking with a pedometer increasing daily the step count by 5–10%, up to 12,000 steps | Moderate intensity (60–70% HR) | Home-based | After chemotherapy and/or radiotherapy + Calcitriol supplementation | Usual care |
Tabatabai et al. J. Clin. Endocrinol. Metab. 2016 [37] | CET |
| 12 months | Three times per week | AET: 20–30 min; RET: one set of 13 exercises, completing eight repetitions, up to two sets of exercises with 8–12 repetitions | NR | Supervised | After chemotherapy and/or radiotherapy | Monthly health newsletter |
Waltman et al. Osteoporos Int. 2010 [38] | RET |
| 24 months |
| 30–45 min. two sets x 8–12 repetitions of exercises | increased weights based on individual response, adding weights after two consecutive training sessions at the maximum set and repetition |
| After chemotherapy and/or radiotherapy + Risedronate, calcium, and Vitamin D | Risedronate, calcium, and Vitamin D |
Winters-Stone et al. Breast Cancer Res Treat. 2011 [39] | RET + IET |
| 12 months | Two supervised session/wk + 1 home-based session/wk | 45–60 min | RET: 60–70% of 1-RM for 1–3 sets of 8–12 rep; progressive increase by increasing band thickness, squat and lunge depth, and sets and repetitions | Supervised and home-based | After chemotherapy and/or radiotherapy | Type of activity: whole body stretching and relaxation exercises Exercise modality: in a seated or lying position to minimize weight-bearing forces Protocol duration: 12 months Frequency: 2 supervised session/wk + 1 home-based session/wk Volume (session): 45–60 min Intensity: NR Supervised and home-based After chemotherapy and/or radiotherapy |
Winters-Stone et al. Osteoporos Int. 2013 [40] | RET + IET |
| 12 months | Two supervised session/wk + 1 home-based session/wk | 45–60 min | RET: 60–70% of 1-RM for 1–3 sets of 8–12 rep; progressive increase by increasing band thickness, squat and lunge depth, and sets and repetitions | Supervised and home-based | After chemotherapy and/or radiotherapy | Type of activity: whole body stretching and relaxation exercises Exercise modality: in a seated or lying position to minimize weight-bearing forces Protocol duration: 12 months Frequency: two supervised session/wk + one home-based session/wk Volume (session): 45–60 min Intensity: NR Supervised and home-based After chemotherapy and/or radiotherapy |
Authors Journal Year | Results | ||
---|---|---|---|
Intragroup Analysis—IG | Intragroup Analysis—CG | Intergroups Analysis | |
Baker et al. Integr. Cancer Ther. 2018 [31] | Molecular biomarkers NTX/Cr (BCE/mmol Cr): 43.3 ± 20.0 vs. 45.9 ± 25.6; p = NR P1NP (μg/L): 62.3 ± 27.0 vs. 64.0 ± 25.6; p = NR | Molecular biomarkers NTX/Cr (BCE/mmol Cr): 39.0 ± 16.4 vs. 38.7 ± 12.9; p = NR P1NP (μg/L): 62.2 ± 25.3 vs. 59.5 ± 26.2; p = NR | Molecular biomarkers NTX/Cr (BCE/mmol Cr): 45.9 ± 25.6 vs. 38.7 ± 12.9; p = 0.929 P1NP (μg/L): 64.0 ± 25.6 vs. 59.5 ± 26.2; p = 0.286 |
De Paulo et al. Exp. Gerontol. 2018 [32] | Molecular Biomarkers CTX (ng/mL): 0.46 ± 0.2 vs. 0.46 ± 0.2; p = NS Osteocalcin (ng/mL): 19 ± 8 vs. 20 ± 9; p< 0.05 Bone Mineral Density Whole body BMD (g/cm2) 1.1 ± 0.1 vs. 1.1 ± 0.1; p = NS Lumbar spine BMD (g/cm2) 1.1 ± 0.1 vs. 1.0 ± 0.1; p = NS Total Hip BMD (g/cm2) 0.9 ± 0.1 vs. 0.9 ± 0.1; p = NS Trochanter BMD (g/cm2) 0.8 ± 0.1 vs. 0.9 ± 0.08; p = NS | Molecular Biomarkers CTX (ng/mL): 0.40 ± 0.1 vs. 0.33 ± 0.2; p = NS Osteocalcin (ng/mL): 17 ± 5 vs. 17 ± 6; p = NS Bone Mineral Density Whole body BMD (g/cm2) 1.1 ± 0.08 vs. 1.1 ± 0.1; p = NS Lumbar spine BMD (g/cm2) 1.1 ± 0.1 vs. 1.0 ± 0.1; p = NS Total Hip BMD (g/cm2) 0.9 ± 0.1 vs. 0.9 ± 0.1; p = NS Trochanter BMD (g/cm2) 0.9 ± 0.1 vs. 0.9 ± 0.1; p = NS | Molecular Biomarkers CTX (ng/mL): 0.46 ± 0.2 vs. 0.33 ± 0.2; p = 0.11 Osteocalcin (ng/mL): 20 ± 9 vs. 17 ± 6; p = 0.14 Bone Mineral Density Whole body BMD (g/cm2) 1.1 ± 0.1 vs. 1.1 ± 0.1; p = 0.5 Lumbar spine BMD (g/cm2) 1.0 ± 0.1 vs. 1.0 ± 0.1; p = 0.65 Total Hip BMD (g/cm2) 0.9 ± 0.1 vs. 0.9 ± 0.1; p = 0.54 Trochanter BMD (g/cm2) 0.9 ± 0.08 vs. 0.9 ± 0.1; p = 0.51 |
Dieli-Conwright et al. Breast Cancer Res. 2018 [33] | Molecular Biomarkers Osteocalcin (ng/mL): 12.1 ± 3.1 vs. 15.0 ± 4.1; p = 0.01 BSAP (ng/mL): 16.1 ± 4 vs. 18.0 ± 5.0; p = 0.01 CTX (ng/mL): 0.48 ± 0.1 vs. 0.44 ± 0.2; p = 0.07 NTX (nM BCE/L): 18.6 ± 3.1 vs. 17.7 ± 2.8; p = 0.10 RANK (pg/mL): 27.4 ± 6.8 vs. 26.7 ± 6.4; p = 0.14 RANKL (pmol/L): 142.5 ± 18.9 vs. 146.1 ± 16.1; p = 0.09 Bone Mineral Density Whole body BMD (g/cm2): 1.22 ± 0.1 vs. 1.27 ± 0.1; p = 0.15 Lumbar spine BMD (g/cm2): 1.16 ± 0.09 vs. 1.20 ± 0.09; p = 0.09 Total Hip BMD (g/cm2): 0.91 ± 0.09 vs. 0.94 ± 0.09; p = 0.17 Trochanter BMD (g/cm2): 0.72 ± 0.07 vs. 0.74 ± 0.07; p = 0.18 Femoral neck BMD (g/cm2): 0.88 ± 0.1 vs. 0.90 ±0.1; p = 0.21 | Molecular Biomarkers Osteocalcin (ng/mL): 12.3 ± 3.4 vs. 12.0 ± 3.0; p = 0.61 BSAP (ng/mL): 16.2 ± 4.3 vs. 15.9 ± 4.2; p = 0.55 CTX (ng/mL): 0.47 ± 0.1 vs. 0.48 ± 0.2; p = 0.74 NTX (nM BCE/L): 18.4 ± 2.7 vs. 18.3 ± 2.5; p = 0.67 RANK (pg/mL): 26.9 ± 6.6 vs. 26.4 ± 6.5; p = 0.34 RANKL (pmol/L): 139.8 ± 18.1 vs. 148.8 ± 18.9; p = 0.47 Bone Mineral Density Whole body BMD (g/cm2): 1.20 ± 0.1 vs. 1.19 ± 0.1; p = 0.29 Lumbar spine BMD (g/cm2): 1.15 ± 0.09 vs. 1.14 ± 0.09; p = 0.57 Total Hip BMD (g/cm2): 0.90 ± 0.09 vs. 0.89 ± 0.08; p = 0.23 Trochanter BMD (g/cm2): 0.71 ± 0.06 vs. 0.70 ± 0.06; p = 0.43 Femoral neck BMD (g/cm2): 0.87 ± 0.1 vs. 0.86 ± 0.1; p = 0.23 | Molecular Biomarkers Osteocalcin (ng/mL): 15.0 ± 4.1 vs. 12.0 ± 3.0; MD: 3.1 (5.6 to 1.5); p = 0.01 BSAP (ng/mL): 18.0 ± 5.0 vs. 15.9 ± 4.2; MD: 1.9 (2.4 to 0.55); p = 0.001 CTX (ng/mL): 0.44 ± 0.2 vs. 0.48 ± 0.2; MD: −0.04 (−0.10 to −0.06); p = 0.10 NTX (nM BCE/L): 17.7 ± 2.8 vs. 18.3 ± 2.5; MD: −0.90 (−1.1 to −0.6); p = 0.12 RANK (pg/mL): 26.7 ± 6.4 vs. 26.4 ± 6.5; MD: −0.70 (−0.9 to −0.4); p = 0.20 RANKL (pmol/L): 146.1 ± 16.1 vs. 148.8 ± 18.9; MD: 3.6 (5.1 to 1.2); p = 0.14 Bone Mineral Density Total BMD (g/cm2): 1.27 ± 0.1 vs. 1.19 ± 0.1; MD: 0.05 (0.04 to 0.02); p = 0.15 Lumbar spine BMD (g/cm2): 1.20 ± 0.09 vs. 1.14 ± 0.09; MD: 0.04 (0.03 to 0.01); p = 0.10 Hip BMD (g/cm2): 0.94 ± 0.09 vs. 0.89 ± 0.08; MD: 0.03 (0.03 to 0.00); p = 0.18 Trochanter BMD (g/cm2): 0.74 ± 0.07 vs. 0.70 ± 0.06; MD: 0.02 (0.03 to 0.00); p = 0.22 Femoral neck BMD (g/cm2): 0.90 ± 0.1 vs. 0.86 ± 0.1; MD: 0.02 (0.03 to 0.00); p = 0.21 |
Kim et al. Cancer Nurs. 2016 [34] | Molecular biomarkers NTX/Cr (nmol/mmol Cr): 45.98 ± 17.58 vs. 52.26 ± 17.78; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.958 ± 0.080 vs. 0.966 ± 0.084; p = NR Total Hip BMD (g/cm2): 0.870 ± 0.089 vs. 0.876 ± 0.083; p = NR Femoral neck BMD (g/cm2): 0.797 ± 0.076 vs. 0.795 ± 0.075; p = NR | Molecular biomarkers NTX/Cr (nmol/mmol Cr): 47.85 ± 23.92 vs. 55.73 ± 26.86; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.987 ± 0.064 vs. 0.985 ± 0.065; p = NR Total Hip BMD (g/cm2): 0.846 ± 0.075 vs. 0.845 ± 0.066; p = NR Femoral neck BMD (g/cm2): 0.798 ± 0.073 vs. 0.805 ± 0.080; p = NR | Molecular biomarkers NTX/Cr (nmol/mmol Cr): 52.26 ± 17.78 vs. 55.73 ± 26.86; p = 0.498 Bone mineral density Lumbar spine BMD (g/cm2): 0.966 ± 0.084 vs. 0.985 ± 0.065; p = 0.246 Total Hip BMD (g/cm2): 0.876 ± 0.083 vs. 0.845 ± 0.066; p = 0.506 Femoral neck BMD (g/cm2): 0.795 ± 0.075 vs. 0.805 ± 0.080; p = 0.352 |
Peppone et al. Clin. Breast Cancer 2010 [36] | Molecular biomarkers BSAP (μg/L): 8.34 ± 0.8 vs. 10.21 ± 1.1; p = NR NTX (nmBCE): 17.6 ± 3.7 vs. 11.1 ± 2.9; p = NR | Molecular biomarkers BSAP (μg/L): 7.64 ± 0.7 vs. 8.12 ± 1.1; p = NR NTX (nmBCE): 20.8 ± 3.3 vs. 18.8 ± 2.5; p = NR | Molecular biomarkers BSAP (μg/L): 10.21 ± 1.1 vs. 8.12 ± 1.1; p = 0.17 NTX (nmBCE): 11.1 ± 2.9 vs. 18.8 ± 2.5; p = 0.14 |
Peppone et al. Support. Care Cancer 2018 [35] | Molecular biomarkers NTX (nmBCE): 13 vs. 13.3; p = NR BSAP (ng/mL): 12.9 vs. 14.7; p = NR | Molecular biomarkers NTX (nmBCE): 12.8 vs. 14.3; p = NR BSAP (ng/mL): 12.2 vs. 13.8; p = NR | Molecular biomarkers NTX (nmBCE): 13.3 vs. 14.3; p = 0.86 BSAP (ng/mL): 14.7 vs. 13.8; p = 0.49 |
Tabatabai et al. J. Clin. Endocrinol. Metab. 2016 [37] | Molecular biomarkers Osteocalcin: NR (decreased); p < 0.05 P1NP: NR (decreased); p < 0.05 NTX/Cr: NR (decreased); p < 0.05 CTX: NR (decreased); p < 0.05 Bone mineral density Lumbar spine BMD (g/cm2): MD: 0.001 ± 0.005; p = NS Total Hip BMD (g/cm2): NR; NS Femoral BMD (g/cm2): NR; NS | Molecular biomarkers Osteocalcin: NR (decreased); p < 0.05 P1NP (decreased): NR; p < 0.05 NTX/Cr: NR (decreased); p < 0.05 CTX: NR (decreased); p < 0.05 Bone mineral density Lumbar spine BMD (g/cm2): MD: −0.014 ± 0.005; p = 0.03 Total Hip BMD (g/cm2): NR; NS Femoral BMD (g/cm2): NR; NS | Molecular biomarkers Osteocalcin: NR; NS P1NP: NR; NS NTX/Cr: NR; NS CTX: NR; NS Bone mineral density Femoral BMD (g/cm2): NR; NS Lumbar spine BMD (g/cm2): NR; NS Hip BMD (g/cm2): NR; NS |
Waltman et al. Osteoporos Int. 2010 [38] | Molecular biomarkers BSAP (%MD): −11.10% ± 2.3; p < 0.001 NTX (%MD): −23.20% ± 2.8; p < 0.001 Bone mineral density Lumbar spine BMD (%MD): 3.08 ± 0.44; p < 0.0001 Total Hip BMD (%MD): 2.15 ± 0.28; p < 0.0001 Femoral neck BMD (%MD): 0.92 ± 0.50; p = 0.06 Radius (33%) BMD (%MD): −0.18 ± 0.41; p = 0.66 Total radius BMD (%MD): −0.27 ± 0.60; p = 0.66 | Molecular biomarkers BSAP (%MD): −08.70 ± 2.6; p < 0.001 NTX (%MD): −16.70 ± 3.3; p < 0.001 Bone mineral density Lumbar spine BMD (%MD): 2.85 ± 0.40; p < 0.0001 Total Hip BMD (%MD): 1.81 ± 0.36; p < 0.0001 Femoral neck BMD (%MD): 0.63 ± 0.42; p = 0.14 Radius (33%) BMD (%MD): −0.16 ± 0.56; p = 0.77 Total radius BMD (%MD): −0.57 ± 0.61; p = 0.35 | Molecular biomarkers BSAP (%MD): −11.10 ± 2.3 vs. −08.70 ± 2.6; p = NR NTX (%MD):−23.20 ± 2.8 vs. −16.70 ± 3.3; p = NR Bone mineral density Lumbar spine BMD (%MD): 3.08 ± 0.44 vs. 2.85 ± 0.40; p = NR Total Hip BMD (%MD): 2.15 ± 0.28 vs. 1.81 ± 0.36; p = NR Femoral neck BMD (%MD):0.92 ± 0.50 vs. 0.63 ± 0.42; p = NR Radius (33%) BMD (%MD): −0.18 ± 0.41 vs. −0.16 ± 0.56; p = NR Total radius BMD (%MD): −0.27 ± 0.60 vs. −0.57 ±0.61; p = NR |
Winters-Stone et al. Breast Cancer Res Treat. 2011 [39] | Molecular biomarkers Osteocalcin (ng/mL): 12.6 ± 4.4 vs. 12.8 ± 3.8; p = NR Deoxypyridinoline (mMol/mMolCr): 21.4 ± 9.8 vs. 13.1 ± 4.2; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.983 ± 0.146 vs. 0.987 ± 0.146; p = NR Total Hip BMD (g/cm2): 0.863 ± 0.101 vs. 0.860 ± 0.105; p = NR Trochanter BMD (g/cm2): 0.657 ± 0.088 vs. 0.654 ± 0.087; p = NR Femoral neck BMD (g/cm2): 0.731 ± 0.100 vs. 0.721 ± 0.101; p = NR | Molecular biomarkers Osteocalcin (ng/mL): 11.3 ± 4.1 vs. 14.3 ± 5.0; p = NR Deoxypyridinoline (mMol/mMolCr): 17.1 ± 5.6 vs. 12.2 ± 3.1; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.971 ± 0.120 vs. 0.949 ± 0.108; p = NR Total Hip BMD (g/cm2): 0.848 ± 0.099 vs. 0.841 ± 0.096; p = NR Trochanter BMD (g/cm2): 0.642 ± 0.091 vs. 0.641 ± 0.089; p = NR Femoral neck BMD (g/cm2): 0.728 ± 0.091 vs. 0.713 ± 0.082; p = NR | Molecular biomarkers Osteocalcin (ng/mL): 12.8 ± 3.8 vs. 14.3 ± 5.0; p = 0.01 Deoxypyridinoline (mMol/mMolCr): 13.1 ± 4.2 vs. 12.2 ± 3.1; p = 0.22 Bone mineral density Lumbar spine BMD (g/cm2): 0.987 ± 0.146 vs. 0.949 ± 0.108; p < 0.01 Total Hip BMD (g/cm2): 0.860 ± 0.105 vs. 0.841 ± 0.096; p = 0.13 Trochanter BMD (g/cm2): 0.654 ± 0.087 vs. 0.641 ± 0.089; p = 0.15 Femoral neck BMD (g/cm2): 0.721 ± 0.101 vs. 0.713 ± 0.082; p = 0.27 |
Winters-Stone et al. Osteoporos Int. 2013 [40] | Molecular biomarkers Osteocalcin (ng/mL): 10.6 ± 4.07 vs. 9.78 ± 4.5; p = NR Deoxypyrodinoline (nmol/mmol Cr): 13.0 ± 4.95 vs. 15.8 ± 12.1; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.983 ± 0.113 vs. 0.972 ± 0.119; p = NR Total Hip BMD (g/cm2): 0.909 ± 0.095 vs. 0.899 ± 0.096; p = NR Trochanter BMD (g/cm2): 0.689 ± 0.065 vs. 0.683 ± 0.066; p = NR Femoral neck BMD (g/cm2): 0.809 ± 0.11 vs. 0.804 ± 0.108; p = NR | Molecular biomarkers Osteocalcin (ng/mL): 14.0 ± 3.78 vs. 11.9 ± 5.5; p = NR Deoxypyrodinoline (nmol/mmol Cr): 14.2 ± 4.57 vs. 15.0 ± 8.6; p = NR Bone mineral density Lumbar spine BMD (g/cm2): 0.988 ± 0.118 vs. 0.970 ± 0.126; p = NR Total Hip BMD (g/cm2): 0.892 ± 0.119 vs. 0.887 ± 0.119; p = NR Trochanter BMD (g/cm2): 0.666 ± 0.099 vs. 0.662 ± 0.101; p = NR Femoral neck BMD (g/cm2): 0.781 ± 0.093 vs. 0.773 ± 0.095; p = NR | Molecular biomarkers Osteocalcin (ng/mL): 9.78 ± 4.5 vs. 11.9 ± 5.5; p = 0.22 Deoxypyrodinoline (nmol/mmol Cr): 15.8 ± 12.1 vs. 15.0 ± 8.6; p = 0.39 Bone mineral density Lumbar spine BMD (g/cm2): 0.972 ± 0.119 vs. 0.970 ± 0.126 p = 0.18 Total Hip BMD (g/cm2): 0.899 ± 0.096 vs. 0.887 ± 0.887; p = 0.65 Trochanter BMD (g/cm2): 0.683 ± 0.066 vs. 0.662 ± 0.101; p = 0.90 Femoral neck BMD (g/cm2): 0.804 ± 0.108 vs. 0.773 ± 0.095; p = 0.68 |
Articles | Domain | Score | ||||
---|---|---|---|---|---|---|
Random Sequence Generation | Appropriate Randomization | Blinding of Participants or Personnel | Blinding of Outcome Assessors | Withdrawals and Dropouts | ||
Baker et al., 2018 [31] | 1 | 1 | 0 | 1 | 1 | 4 |
De Paulo et al., 2018 [32] | 1 | 0 | 0 | 0 | 1 | 2 |
Dieli-Conwright et al., 2018 [33] | 1 | 1 | 0 | 0 | 1 | 3 |
Kim et al., 2016 [34] | 1 | 1 | 0 | 1 | 1 | 4 |
Peppone et al., 2010 [35] | 1 | 1 | 0 | 0 | 1 | 3 |
Peppone et al., 2018 [36] | 1 | 1 | 0 | 0 | 1 | 3 |
Tabatabai et al., 2016 [37] | 1 | 1 | 0 | 1 | 1 | 4 |
Waltman et al., 2010 [38] | 1 | 0 | 0 | 0 | 1 | 2 |
Winters-Stone et al., 2011 [39] | 1 | 0 | 0 | 1 | 1 | 3 |
Winters-Stone et al., 2013 [40] | 1 | 0 | 0 | 1 | 1 | 3 |
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de Sire, A.; Lippi, L.; Marotta, N.; Folli, A.; Calafiore, D.; Moalli, S.; Turco, A.; Ammendolia, A.; Fusco, N.; Invernizzi, M. Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2023, 24, 921. https://doi.org/10.3390/ijms24020921
de Sire A, Lippi L, Marotta N, Folli A, Calafiore D, Moalli S, Turco A, Ammendolia A, Fusco N, Invernizzi M. Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2023; 24(2):921. https://doi.org/10.3390/ijms24020921
Chicago/Turabian Stylede Sire, Alessandro, Lorenzo Lippi, Nicola Marotta, Arianna Folli, Dario Calafiore, Stefano Moalli, Alessio Turco, Antonio Ammendolia, Nicola Fusco, and Marco Invernizzi. 2023. "Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 24, no. 2: 921. https://doi.org/10.3390/ijms24020921