Osteoporosis International (2023) 34:15–28

https://doi.org/10.1007/s00198-022-06592-8

REVIEW

Exercise and the prevention of major osteoporotic fractures in adults:

a systematic review and meta‑analysis with special emphasis
on intensity progression and study duration
Isabelle Hoffmann1,2 · Matthias Kohl2,3,4 · Simon von Stengel1,2,4 · Franz Jakob2,4,5 · Katharina Kerschan‑Schindl2,4,6 ·
Uwe Lange2,4,7 · Stefan Peters2,4,8 · Daniel Schoene1,2,4 · Cornel Sieber2,4,9 · Friederike Thomasius2,4,10 ·
Heike A. Bischoff‑Ferrari2,11,12 · Michael Uder2,4,13 · Wolfgang Kemmler1,2,4,13

Received: 14 February 2022 / Accepted: 26 October 2022 / Published online: 10 November 2022
© The Author(s) 2022

Abstract
Summary The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized
exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of
osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration.
Introduction Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient
agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet
to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic
fractures in adults.
Methods We conducted a systematic search of six literature databases according to the PRISMA guideline that included
controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG)
and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses
were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months).
Results In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included.
The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75,
95% CI: 0.54–0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did
not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity
among the trials of the subgroups ­(I2 ≤ 0–7.1%) was negligible.
Conclusion The present systematic review and meta-analysis provided significant evidence for the favorable effect of exer-
cise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction
of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions.
PROSPERO ID: CRD42021250467.

Keywords Exercise training · Intensity progression · Major osteoporotic fractures · Study duration

Introduction 10–15 years [1]. A large variety of pharmaceutic agents tar-

get osteoporosis, most of which are very cost intensive, have
Low-trauma fractures related to osteoporosis are a major potential negative adverse effects, and focus predominately
problem in our aging society. Considering the demographic on the bone. In contrast, physical exercise is a low-cost
change in Europe, the number of osteoporotic fractures approach providing positive effects on fall risk [2] and bone
will quite likely increase by about 25% during the next strength [3, 4] without causing relevant adverse effects [5].
Thus, exercise might be an excellent strategy for combat-
ting fractures in older adults. Reviewing the literature shows
* Wolfgang Kemmler that there is indeed some evidence for a fracture-preventing
wolfgang.kemmler@imp.uni-erlangen.de effect of exercise in older adults [6–9]. However, with the
Extended author information available on the last page of the article exception of an older systematic review and meta-analysis

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16 Osteoporosis International (2023) 34:15–28

that focused on low-trauma overall fractures [7], all the other Eligibility criteria
studies [6, 8, 9] focused on data regarding fall-related frac-
tures. In a recent systematic review and meta-analysis, we Briefly, randomized and non-randomized clinical studies were
determined significant positive effects of exercise on overall included that fulfilled the following eligibility criteria: (a) exer-
and major osteoporotic fracture incidence [10]. Neverthe- cise studies on fracture prevention, fall reduction, and bone
less, due to the considerable heterogeneity between the trial strength with (b) at least one exercise (EG) versus one control
results, it is important to identify key components of promis- group (CG) that (c) reported the number of hip, lumbar spine,
ing exercise protocols. While their close interaction might forearm, and/or humerus fractures (d) separately for EG and CG,
prevent a meaningful sub-analysis of many exercise param- independently of (e) whether fractures were defined as primary
eters (e.g., exercise intensity), we focus on intensity progres- or secondary outcome, observation, or adverse event, and (e)
sion during the trial and study duration, as these may well be female and male cohorts older than 50 years on average that were
more independent training parameters. Thus, besides provid- observed (f) for at least 3 months (i.e., study length ≥ 3 months).
ing evidence for a (osteoporotic) fracture-preventing effect Studies that supplied (a) pharmaceutic agents (e.g., gluco-
of exercise, we concentrated on the corresponding effect of corticoids, bisphosphonates) or treatments (e.g., chemo- and/
(1) the progression of intensity during exercise intervention or radiotherapy) with relevant impact on bone metabolism, (b)
and (2) the duration of the study intervention,1 in order to trials/study groups with mixed interventions other than exercise
derive reliable exercise recommendations. and low-dosed calcium/cholecalciferol were excluded. We also
excluded review articles, case reports, editorials, conference
abstracts, letters, preliminary data, or duplicate studies. For the
Methods present subgroup analyses, studies (i.e., [12–14]) that terminated
their intervention 6 months ago and longer were not considered.
This systematic review and meta-analysis is part of the Aus-
tria/German/Swiss (DACH) S3 Guideline “körperliches Data extraction
Training zur Frakturprophylaxe” (AWMF: 183—002).
During the first step, two reviewers (IH, MS) independently
Literature search reviewed the titles and abstracts for eligible articles. Sub-
sequently, full-text articles were reviewed by IH and WK.
We adopted the Preferred Reporting Items for Systematic Eligible articles were extracted by IH and WK using a
Reviews and Meta-Analyses (PRISMA) statement [11]. detailed extraction form that asked for study characteris-
Briefly, we checked six electronic databases (PubMed, tics, study protocol, participant and exercise characteris-
Scopus, Web of Science, Cochrane, Science Direct, and tics, supplementation, and fractures in the EG and CG. In
ERIC) without language restrictions for articles published the case of missing information, the authors in question
from January 1, 2013 (last search [7]) to May 2021. We were contacted (n = 6).
applied keywords and their synonyms around the queries
“Bone mass” or “Osteopenia” or “Bone turnover” or “Bone Outcome measures
metabolism” or “Bone mineral content” or “Skeleton” or
“Bone Mineral Density” or “BMD” or “Bone Density” or As per FRAX [15], low-trauma fractures of the arm, fore-
“Osteoporoses” or “Osteoporosis” or “Bone structure” or arm, or wrist and hip and vertebral fractures were summa-
“Bone status” or “Bone Tissue” or “bone”) AND (“Bone rized into major osteoporotic fracture as the primary study
fracture” or “Fracture” or “fragility fracture” or “Broken outcome of the present study. Fractures induced by falls from
Bone”) AND (“Exercise” or “physical activity” or “Physi- levels higher than standing and car or bicycle accidents were
cal training” or “Exercise training”) AND (“clinical trial”) not included. However, in a minor variation from FRAX,
AND (“45 years and older”). We also checked reference all types of humerus and vertebral fractures were included.
lists of eligible studies and systematic reviews/meta-analysis
that focused on fracture and fall reduction and bone-related Quality assessment
outcomes (e.g., BMD). Studies without full texts were not
considered. The Physiotherapy Evidence Database (PEDro) scale risk
of bias tool [16] and the TESTEX (Tool for the assEssment
of Study qualiTy and reporting in Exercise) score [17] spe-
1
cifically dedicated to evaluate the methodologic quality of
More precisely, the studies listed the length of the intervention as
“study duration.” Since no included study reported a delay between
physiotherapy and exercise trials was used to rate methodo-
baseline or follow-up assessment and start or end of the intervention, logic quality of the exercise trials.
we consistently use the term “study duration.”.

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Osteoporosis International (2023) 34:15–28 17

Fig. 1  Flow-chart of the present

systematic review according to
PRISMA [11]

Data synthesis described in data synthesis above. All tests were 2-tailed,
and significance was accepted at p < 0.05.
Of importance, we pooled the three different exercise
groups of Karinkanta et al. [18] into one exercise group.
With respect to the study of Bischoff-Ferrari et al. [19], we Results
included the isolated exercise group (without vitamin D)
with data provided by the authors. As stated, we focused on Our search identified 11 eligible studies [18, 19, 24–32]
two research issues, intensity progression and duration of the (Fig. 1) with a pooled number of participant years of
exercise study in the sub-analyses. Two reviewers (IH, WK) n = 9715 in the EG and n = 9592 in CG. All studies included
independently categorized the trials into the subgroups, with community dwelling middle-aged to older cohorts.
full consensus for classification. Table 1 gives a summary of the study and participant
characteristics. In summary, no relevant between group dif-
Statistical analysis ferences (EG vs. CG) were observed for baseline participant
characteristics of the individual studies. Initial sample sizes
We used the mixed-effects conditional Poisson regression varied from 27 to 3279 participants/group. All but two stud-
model suggested by Stijnen et al. [20] for our analysis. We ies [24, 32] included Caucasian cohorts on average between
applied R packages metafor [21] included in the statistical 54 ± 3 {Chan, 2004 #8453} and 80 ± 4 {Sakamoto, 2013
software R [22]. The incidences were transformed into inci- #15970} years of age. Seven studies focused exclusively on
dence rate ratios (IR) along with 95% confidence intervals women. Six studies defined fracture risk as the primary out-
(95% CI). Heterogeneity between studies was checked using come (Table 1).
­I2 statistics2 [23] in combination with a Wald and likelihood
ratio test, respectively. Funnel plots with Kendall’s τ statis- Exercise characteristics
tic were applied to explore potential small study/publica-
tion bias. Subgroup analyses were applied for subgroups as Table 2 displays exercise characteristics of the included stud-
ies. The exercise program of three studies focused predomi-
nately on combined fall prevention/bone strengthening [25,
2
0–40%, low; 30–60%, moderate; 50–90%, substantial; 75–100%, 27, 28] or fall prevention protocols [26, 30, 32], while four
considerable heterogeneity. studies [18, 24, 29, 31] concentrated on bone strengthening

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Table 1  Study and participant characteristics of the included studies

First author, Study Age [years], Female Body Mass Initial sam- Dropout Specific character- Medication Fracture as
year, study- length status gender Index, [kg/ ple size [n] [%] istics of the study (%)a the primary
type [months] m2] group outcome

Bischoff- 36 75 ± 4 EG: 62% 26.3 ± 4.2 EG: 267 Total: 12 No major health EG: ≥ 48 Yes
Ferrari cdw CG: 62% 26.4 ± 4.4 GC: 270 events, suffi- CG: ≥ 51
et al. ciently mobile,
2020, good cognitive
RCT​ status, ≥ 40%
with fall history
Chan et al. 12 54 ± 3 EG: 100% 24.1 ± 4.7 EG: 67 EG: 19 Early-postmeno- none No
2004, cdw CG: 100% 23.5 ± 4.6 GC: 65 GC: 17 pausal healthy
RCT​ women without
a history of
fractures
Ebrahim 24 67 ± 8 EG: 100% n.g EG: 81 Total: 41 Women with upper n.g No
et al. n.g CG: 100% GC: 84 limb fractures
1997, during the last
RCT​ 2 years
Gill et al. 31 79 ± 5 EG: 67% 30.1 ± 5.7 EG: 818 n.g Functional EG: 5.3b Yes?c
2016, n.g CG: 67% 30.3 ± 6.2 CG: 817 limitations CG: 5.4
RCT​ (SPPB ≤ 9; but
400 m ≤ 15 min)
Karinkanta 12 70–79 EG: 100% 28.1 ± 3.8 EG: 112 EG: 4 No diseases or none No
et al., cdw CG: 100% 29.6 ± 3.7 CG: 37 GC: 3 medication
2007, relevantly affect-
RCT​ ing falls or bone
strength, no
osteoporosis
Kemmler 18 69 ± 4 EG: 100% 26.1 ± 4.0 EG: 123 EG: 7 No diseases or none No
et al., cdw CG: 100% 26.9 ± 4.3 CG: 124 CG: 9 medication
2010, relevantly affect-
RCT​ ing falls or bone
strength
Kemmler 16 yrs 55 ± 3 EG: 100% 25.7 ± 3.4 EG: 86 EG: 31 Early-postmen- none Yes
et al., cdw CG: 100% 25.3 ± 4.2 GC: 51 CG: 9 opausal (1–8
2015, CT y) women with
osteopenia; no
diseases/medica-
tion relevantly
affecting falls or
bone strength
Korpelainen 30 70–73 EG: 100% 25.7 ± 3.4 EG: 84 EG: 18 Low BMD at the n.g No
et al., cdw CG: 100% 25.5 ± 3.5 CG: 76 GC: 12 proximal femur
2006, or distal radius
RCT​ (< -2 SD-T-
score)
Lamb et al., 18 78 ± 6 EG: 53% 27 ± 5 EG: 3279 EG1: 16 People at increased n.g Yes
2020, cdw CG: 52% 26 ± 5 GC: 3223 CG: 14 risk for falls
cluster- (falls risk screen-
RCT​ ing question-
naire)
Preisinger 48 61 ± 7 EG: 100% n.g EG: 27 EG: 56 Moderate back n.g No
et al. cdw CG: 100% GC: 31 GC: 0 complaints, no
­1996d, medication rel-
RCT​ evantly affecting
bone strength

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Table 1  (continued)
First author, Study Age [years], Female Body Mass Initial sam- Dropout Specific character- Medication Fracture as
year, study- length status gender Index, [kg/ ple size [n] [%] istics of the study (%)a the primary
type [months] m2] group outcome
Sakamoto 6 ca. 80 ± 4 EG: 79% 23.2e EG:714 EG: 43 Subjects with n.g Yes
et al., cdw CG: 83% 23.2 GC: 651 CG: 30 leg standing
2012, time ≤ 15 s; no
RCT​ other conditions
relevantly affect-
ing fall risk

Cdw community dwelling, CT controlled trial, FaME fall management exercise, n.g. not given, OEP Otago Exercise Program, RCT​randomized
controlled trial
a
Only medication with moderate impact on falls or bone strength
b
Overall number of drugs
c
Serious fall injury: “fall resulting in a clinical non-vertebral fracture or that led to hospital admission”
d
We included the “fully compliant subgroup”
e
…calculated from body height and mass

only. Length of the exercise intervention ranged from Meta‑analysis results

6 months [32] to 16 years [28]. Unfortunately, not all of
the studies reported the exercise intensity applied for the The meta-analysis demonstrated a significant (p = 0.006)
respective training component adequately and comprehen- effect of exercise on major osteoporotic fractures (IR: 0.75;
sively (Table 2). With respect to physical interventions in the 95% CI: 0.59–0.94) (Figs. 2 and 3, lower part). Heterogene-
control group, at least three studies [19, 25, 27] implemented ity between the trials ­(I2 < 1%) was negligible, and funnel
an “active control group.” plots and tests for funnel plot asymmetry indicate no relevant
evidence for publication/small study bias.
Supplementation with vitamin D and/or calcium
Subgroup analysis on exercise components
Two studies [27, 28] provided calcium (up to 1000 mg/d)
supplements for the EG and CG. Progression of intensity during the exercise trial

Methodological quality Five studies provided intensity progression in their exer-

cise protocols [18, 26–29], while another six studies did not
The methodological quality is listed in Table 3. Score change exercise intensity during the intervention (Table 2,
points applying PEDro vary between 3 and 9 from a Fig. 2). While we observed more favorable effects in the sub-
maximum of 10 (9) points and 6–14 from a maximum groups that applied progression of intensity, in summary, we
of 15 when applying the TESTEX score. Of importance, did not determine a significant difference between the two
blinding of instructors (i.e., treatment providers) is not subgroups (p = 0.133) (Fig. 2). Heterogeneity between the
applicable in exercise studies; consequently, the maximum trials was negligible for both subgroups (­ I2 = 0% and 7.1%).
score for PEDro should be considered 9 points. In contrast,
TESTEX did not score blinding of treatment providers and Duration of the intervention protocol of the exercise
participants. trial
Altogether we observed 151 major osteoporotic frac-
tures (MOF) in the exercise and 196 fractures in the con- Only three studies applied study protocols ≤ 12 months [18,
trol group. Excluding the follow-up studies, 126 MOF 24, 32], while another eight studies exercised > 12 months to
were observed in the EG versus 162 MOF in the CG. In 16 years (Table 2, Fig. 3). In contrast to the shorter studies/exer-
detail, 44 versus 58 hip fractures were recorded in the cise interventions (IR: 0.70; 95% CI: 0.23 to 2.15), we observed
EG vs. CG; in parallel 62 (EG) vs. 52 (CG) forearm and significant effects for the exercise trials of longer duration (IR:
wrist fractures were reported. Unfortunately, some studies 0.77; 95% CI: 0.61 to 0.97); however, in summary, no relevant
did not report vertebral fractures; thus, the number of 25 differences between the two subgroups (p = 0.883) (Fig. 3) were
fractures in the EG vs. 49 in the CG might be considerably observed. Heterogeneity between the trials was negligible for
underreported. both subgroups ­(I2 = 0%).

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Table 2  Exercise characteristics of the included studies

First author, year Fracture prevention Design, supervision Length of Type of exercise in Exercise/strain composi- Progression Attendance rate Intervention in the CG
strategy intervention the EG; supplemen- tion of Intensity

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[months] tation

Bischoff-Ferrari n.g.a IE-PNS 36 DRT; no supple- 3 × 30 min/week, 5 resist- No n.g.b Flexibility, 5 exercises,
et al., 2020 ments ance type exercises (sit- 3 × 30 min/ week
to-stand, one-leg stance,
pull backs, and external
shoulder rotation against
elastic resistance, steps);
no details on strain
composition given
Chan et al., 2004 Bone Strength JE-PS 12 Tai Chi Chun: Yang 5 × 50 min/week; all No 84% No intervention
style; no supple- main muscle groups, no
ments details on strain compo-
sition given
Ebrahim et al., 1997 Bone strength and IE-PNS 24 Brisk walking; no 3 × 40 min/week brisk No 100% Exercises for the upper
fall reduction supplements walking presumably limb; (details n.g.)
with moderate intensity study nurse-visits
(details n.g.)
Gill et al., 2016 Fall prevention IE-PNS 26 Multi-component: In total: 5–6 × ≈30 min/ Yes 63% No physical interven-
walking, lower week; presumably tion, health educa-
extremity DRT, 2–3 × 30 min/week tion program
flexibility exercises walking at RPE 13
for major muscle (Borg CR-20), 3 × week
groups, balance; no 5 DRT exercises 2
supplements sets × 10 reps at RPE
15–16 (Borg CR-20),
10 min of balance
exercise and 3–5 min of
stretching
Karinkanta et al., Bone strength JE-PS 12 DRT for all main 3 × 45–50 min/week; Yes 67% No intervention
2007 muscle groups vs. DRT: 7 exercises, 3
balance and high sets, reps 8–10 reps at
Impact exercise vs. 75–80% 1RM
multi-component:
(DRT, impact, bal-
ance); no supple-
ments
Osteoporosis International (2023) 34:15–28
 Table 2  (continued)
First author, year Fracture prevention Design, supervision Length of Type of exercise in Exercise/strain composi- Progression Attendance rate Intervention in the CG
strategy intervention the EG; supplemen- tion of Intensity
[months] tation

Kemmler et al., 2010 Bone strength/fall JE/IE-PS 18 Multi-component: In total 4 sessions/week; Yes 60% Wellness protocol.
prevention aerobic dance, 2 × 60 min/week JE-S, JE-S: 77% 4 × 10 week/18
DRT, functional aerobic dance at 70–85% IE-NS: 42% 1 × 60 min of mobil-
gymnastics, isomet- HRmax, static/dynamic ity and flexibility
ric exercise; balance exercises, exercise
Up to 500 IU Vit- isometric/floor exercises
D/d; 1000 mg/d Ca at RM, 3 upper body
exercises with 2–3 sets,
Osteoporosis International (2023) 34:15–28

10–15 reps of with

elastic bands at RM-2
reps; 3 leg exercises
with 2 sets with 8 reps
at RM-2reps; IE-NS:
2 × 25 min/week, 8
isometric and dynamic
strength exercises
Kemmler et al., 2015 Bone strength/fall JE/IE-PS 16 yrs Multi-component: In total 4 sessions/ Yes 57% No intervention
prevention High impact aero- week; 2 × 60 min/week JE-S: 83%
bic dance, jumping, JE-S, 20 min of HI IE-NS:31%
DRT, functional aerobic dance at 70–85%
gymnastics, bal- HRmax, 4 × 15 different
ance (last 4 years); jumps; periodized DRT
up to 500 IU/d Vit- 9–13 exercises up to
D, 1000 mg Ca/d 90% 1RM with periods
of high velocity; IE-NS:
2 × 25 min, 8 isometric
and dynamic strength
exercise; 5–6 flexibility
exercises
Korpelainen et al., Bone strength JE/IE-PNS 30 Multi-component: HI JE-S for 6 months/year: Yes < 50% No physical inter-
2006 aerobic exercises, 1 × 60 min + 6 × 20 min/ JE-S: 75% vention, social
jumps, balance, week IE-NS intermitted IE-NS:43% interaction, health
DRT; no supple- by IE-NS (7 × 20 min/ information
ments week); HI exercises,
DRT in circuit mode ≥ 4
exercises, 3 sets of 30 s
of exercise—30 s of
rest, focus on maximum
reps/30 s, shorter ver-
sion during IE-NPS

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Table 2  (continued)
First author, year Fracture prevention Design, supervision Length of Type of exercise in Exercise/strain composi- Progression Attendance rate Intervention in the CG
strategy intervention the EG; supplemen- tion of Intensity

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[months] tation

Lamb et al., 2020 Fall prevention IE-PNS 18 Multi-component: In total ≥ 3 × 30 min/week; No n.g Advice by mail
Otago Exercise 5 DRT-exercises with 4
Program (OEP); intensity levels up to 2
no supplements sets of 10 reps; and 12
balance exercises with 4
levels; up to 4 sets of 10
steps; 2 × 30 min walk-
ing with habitual speed
Preisinger et al., Bone strength/back IE-PNS 48 Physiotherapy incl. ≥ 3 × 20 min/week; No n.a.c No exercise interven-
1996 pain postural stability, resistance exercises with tion partially mas-
motor control, elastic bands on unstable sage, electro-therapy
coordination, surface/seat in EG and CG
functional DRT,
flexibility; no sup-
plements
Sakamoto et al., Fall prevention IE-PNS 6 Balance; no supple- 7 × week, 3 No n.g No intervention
2012 ments sessions/d × 60 s one leg
stand without holding
on an object (when
possible)

Ca calcium, DRT dynamic resistance exercise, IE individual exercise (predominately home-based), JE joint exercise (predominately facility-based), n.a. not applicable, n.g. not given, PNS pre-
dominately non-supervised, PS predominately supervised, RM repetition maximum, RPE rate of perceived exertion, Vit-D cholecalciferol
a
The intervention is more indicative of bone strength, but since bone parameters were not determined, we are unable to decide this issue
b
70% of the participants carried out at least twice per week, 62% carried out at least 3 sessions/week
c
Included were participants that exercised ≥ 3 × 20 min/week (44%)
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Table 3  Methodologic quality of the exercise studies

PEDro-Criteria Additional TESTEX Criteriaa

Blinding assessors

intensity constant

energy expended
Exercise volume &
Total score PEDro
Blinding subjects
Author, year

Intention to treat

Relative exercise
Activity monito-
Between group

Adverse effects
85% allocation
participation≥
homogeneity

comparison

Attendance
concealment

Total score
allocationb

Measure of
Inter group

personnel

ring in CG
variability

reported

reported
analysis c
Blinding
Random

Allocation

TESTEX
Bischoff-Ferrari et al. 2020 8 12
Chan et al. 2004 4 7
Ebrahim et al. 1997 4 7
Gill et al. 2016 7 12
Karinkanta et al.,2007 7 14
Kemmler et al. , 2010 9 14
Kemmler et al. 2015 4 11
Korpelainen et al. 2006 7 13
Lamb et al. 2020 6 11
Preisinger et al. 1996 3 7
Sakamoto et al. 2012 4 7
a
TESTEX awards one point for listing the eligibility criteria and, also in contrast to PEDro, a further point for the between group comparison of
at least one secondary outcome
b
Studies that either have not randomly assigned participants to the groups (-) or retrospectively analyze for training frequency (n.a.)
c
….. or all subjects received treatment or control as allocated (…or were retrospectively analyzed)

Discussion aimed to determine parameters that might explain the

effectiveness of exercise in reducing fractures related to
Apart from generating evidence for the fracture-preventing osteoporosis in middle-aged to older adults. In summary
effect of exercise on low-trauma, major osteoporotic frac- the study provided evidence for a significant (major osteo-
tures [15], the present systematic review and meta-analysis porotic) fracture reducing effect of exercise; however, the

Fig. 2  Forest plot of data on the

effect of “intensity progression
during the trial” on exercise
effects on major osteoporotic
fracture risk

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Fig. 3  Forest plot of data on

the effect of “study/intervention
duration” on exercise effects on
major osteoporotic fracture risk

sub-analysis on the relevance of intensity progression and might be negligible in studies of short duration, but the only
exercise duration on this positive interaction did not sig- study to which this could applied is the 6-month study of
nificantly support the relevance of these important exercise Sakamoto et al. [32]. Another reason for our finding might
parameters/principles. be that progression in particular of balance protocols was
Due to the close interaction of exercise parameters [33] rarely reported and the corresponding studies were thus not
and the few exercise trials that focus on definite outcomes correctly classified by our approach.
of fracture reduction, it is a daunting task to identify key Although this aspect is not negligible for fall prevention
(exercise) parameters for generating meaningful recommen- studies [2] either, it is outweighed by duration of the study/
dations for promising exercise protocols. This refers espe- intervention in exercise programs on bone strengthening
cially to the area of fracture reduction with its fundamentally due to the length of bone adaptation in adults [35, 36].
different training strategies on bone strengthening and/or fall Furthermore, along with high sample sizes, study dura-
reduction [34]. As most exercise parameters (e.g., type of tion is important for generating enough statistical power
exercise, exercise intensity, training frequency) were con- to address fracture number as a clinical outcome [28]. Of
founded by the aspects described above, we focused on the importance only three studies applied exercise protocols
principle of (intensity) progression and the duration of the of 6 [32] to 12 months [18, 24]. Comparing the latter stud-
study intervention because these can be considered superor- ies with longer studies (Fig. 3), we observed comparable
dinate variables of exercise training protocols. effects sizes for the two categories.
Progression, i.e., the frequent adaptation of training load In summary, we provided further evidence for the (osteo-
to persistently apply the overload principle [33], can be porotic) fracture-reducing effect of exercises; however, we
realized by changing several parameters including exercise failed to determine key parameters of promising exercise
frequency and/or intensity, type of exercise, or exercise dura- parameters or training principles in this area. We predomi-
tion. However, with few exceptions [27, 28], most of the nately attribute this unfavorable result to the fact that due to
included exercise trials focused (if at all) on the progression participant characteristics,3 two fundamentally different exer-
of exercise intensity. In summary, we observed more favora- cise strategies, i.e., bone strengthening or fall reduction (or
ble effects of studies that applied intensity progression (vs.
non-progression) on major osteoporotic fracture numbers; 3
E.g., early-postmenopausal osteopenic women with high bone turn-
nevertheless, differences between the subgroups remained over and low risk of falls versus vulnerable older people with mani-
non-significant (Fig. 2). One may argue that progression fest osteoporosis, pharmaceutic therapy, and high fall risk.

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Osteoporosis International (2023) 34:15–28 25

both), can be applied for reducing fracture risk. Considerable of vertebral and humerus fractures under “major osteoporotic
differences in addressing the two training aims confounded a fractures,” which is not consistent with FRAX [15]. (3) We
joint analysis for meaningful exercise parameters and train- included studies with “active control groups” (Table 3) which
ing principles. In parallel, against our expectation, with its might have diluted our exercise effects on fracture reduction
close interaction of exercise parameters, the complexity of slightly. (4) We included one non-randomized controlled trial
exercise might have also confounded our analysis of intensity [28]. Although fully aware of potential sources of bias,6 we
progression and study duration. Since the methodologically included this study due to its long duration (16 years), the suf-
correct approach for addressing this problem, i.e., trials with ficient power to address fracture as an outcome, and “fracture
two exercise arms that differ only in the given component of reduction” being stated as the primary outcome. (5) The latter
interest (e.g., exercise frequency; [37]), was not available4 in aspect might be highly relevant since studies that focus on BMD
the domain of fracture reduction, corresponding exercise rec- effects (“bone-strength,” Table 3) in older people, for example,
ommendations have to be derived from more dedicated meta- did not adequately address all the relevant fracture determinants
analyses in the area of osteoporosis [38–40] or fall reduction and thus may have generated suboptimum results. (6) Heteroge-
[2, 41] or even better: from randomized controlled trials with neity between the trials was consistently negligible (i.e., I­ 2: 0 to
similar or comparable training aims and cohorts. 7.1%) among the subgroups (Figs. 2 and 3). Further funnel plot
Due to higher evidence standards, more dedicated inclusion analyses did not indicate evidence for publication/small-study
criteria, higher fracture risk, and diverging fracture outcomes, it bias. This finding is noteworthy because the studies vary widely
is difficult to set our results into perspective with data on phar- with respect to participant (Table 1) and exercise characteristics
maceutic studies. However, a (very) rough overview on bispho- (Table 2). (7) Finally, the statistical power to address differences
sphonate (risedronate[42],5 zoledronate [43], denosumab [44], between the subgroups can be considered moderate at best. Nev-
and teriparatide [45]) effects on fragility fracture incidence ertheless, a recent (meta-)analysis on major osteoporotic fracture
indicates results in the area of 20% (risedronate, non-vertebral reduction that focused on supervision of the exercise program
fractures) to 54% (teriparatide, overall fragility fractures). Our revealed significant differences in favor of supervised exercise
result falls at the lower range; however, it should be borne in protocols {Hoffmann, 2022 #16145}. Thus, the present analysis
mind that all of these pharmaceutic studies focus on secondary does not seem to be “hopelessly underpowered.”
preventions, i.e., subjects with a much higher fracture prevention
potential. Evidence for a fracture preventing effect in the area
of primary prevention is much lower to negligible (e.g., [42]). Conclusion
From a socioeconomic point of view, on the other hand, it would
be wrong to conclude that exercise might be a true alternative Our systematic review and meta-analysis showed a 23% reduc-
to pharmaceutical therapy. A large proportion of frail elderly tion in major osteoporotic fracture incidence, thus providing
persons, the most vulnerable group for fractures, demonstrate further evidence for the significant favorable effect of exercise
low affinity to exercise [46] and will be hard to persuade to start on (low-trauma) fracture reduction. On the other hand, our
exercising frequently. Nevertheless, the combination of bone joint analysis of exercise protocols that focus on bone strength-
strengthening drugs and fall prevention exercise will definitely ening, fall reduction, or both did not indicate high relevance
be the most promising fracture reduction strategy for this cohort. of intensity progression or study duration. Along with others
Apart from problems described above, other limitations [47], we feel that meta-analyses might not be the best choice
and/or particularities of the present work might have affected for deriving promising exercise recommendations, at least for
our results. (1) We focused on low-trauma fractures and thus the area of fracture reduction due to the complexity of exercise
excluded fractures caused, for example, by bicycle or car acci- and the close interaction of exercise parameters. Well-designed
dents, or falls from levels higher than standing. However, due to and adequately powered randomized controlled trials might be
unavailable data, we might have not included only “low-trauma more suitable to address this issue.
fractures.” However, considering that in osteoporosis not only
Acknowledgements We acknowledge the support of the Elsbeth Bon-
fragility fractures but also all forms of fractures, including hoff Stiftung, Berlin, Germany and the Dachverband Osteologie (DVO)
high-impact trauma fractures, occur quite frequently, this limi- e.V. We are also very grateful to all authors who provided missing
tation might be negligible. (2) We further subsume all types information for the present work. The article was performed in (partial)
fulfillment of the requirements for Isabelle Hoffmann’s obtaining the
degree Dr. med. dent.
4
Certainly due to the need to generate an enormous power (ie num-
ber of participant years) to address fracture number as an outcome
considering further the potentially small differences between the
groups…. 6
While we do not observe differences in prognostic outcome meas-
5
In the area of secondary prevention; effects on primary prevention ures, adherence rates were higher compared to most comparable
were much lower. RCTs.

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26 Osteoporosis International (2023) 34:15–28

Author contribution All authors conceived and designed this system- 6. de Souto BP, Rolland Y, Vellas B, Maltais M (2019) Association
atic review and meta-analysis and drafted and revised the manuscript. of long-term exercise training with risk of falls, fractures, hos-
Article search, screening, data extraction, and rating were performed pitalizations, and mortality in older adults: a systematic review
by IH, MS, SvS, DS, HBF, and WK, and formal analysis was conducted and meta-analysis. JAMA Intern Med 179:394–405. https://​doi.​
by WK and MK. All authors read the final version of the manuscript. org/​10.​1001/​jamai​ntern​med.​2018.​5406
WK accepts direct responsibility for the work. 7. Kemmler W, Haberle L, von Stengel S (2013) Effects of exercise
on fracture reduction in older adults: a systematic review and
Funding Open Access funding enabled and organized by Projekt meta-analysis. Osteoporos Int 24:1937–1950. https://​doi.​org/​
DEAL. This research received no external funding; however, the pro- 10.​1007/​s00198-​012-​2248-7
ject S3-Guideline “körperliches Training zur Frakturprophylaxe” was 8. Wang Q, Jiang X, Shen Y et al (2020) Effectiveness of exercise
supported by the Elsbeth Bonhoff Foundation. intervention on fall-related fractures in older adults: a systematic
review and meta-analysis of randomized controlled trials. BMC
Data availability The data that support the findings of this study Geriatr 20:322. https://​doi.​org/​10.​1186/​s12877-​020-​01721-6
are available from the corresponding author (WK), upon reasonable 9. Zhao R, Feng F, Wang X (2017) Exercise interventions and pre-
request. vention of fall-related fractures in older people: a meta-analysis
of randomized controlled trials. Int J Epidemiol 46:149–161.
Declarations https://​doi.​org/​10.​1093/​ije/​dyw142
10. von Stengel S, Becker C, Gosch M, Jakob F, Kerschan-Schindl
Statement of human rights This article does not cover any studies K, Kladny B, Clausen J, Lange U, Middeldorf S, Peters S, Sch-
with human participants or animals performed by any of the authors. oene D, Sieber C, Tholen R, Thomasius F, Bischoff-Ferrari HA,
Uder M, Kemmler W (2022) Exercise reduces the number of
overall and major osteoporotic fractures in adults. Does supervi-
Conflicts of interest None. sion make a difference? Systematic review and meta-analysis.
J Bone Miner Res. https://​doi.​org/​10.​1002/​jbmr.​4683. Online
Informed consent Not applicable. ahead of print
11. Moher D, Shamseer L, Clarke M et al (2015) Preferred report-
Open Access This article is licensed under a Creative Commons Attri- ing items for systematic review and meta-analysis protocols
bution-NonCommercial 4.0 International License, which permits any (PRISMA-P) 2015 statement. Syst Rev 4:1. https://​doi.​org/​10.​
non-commercial use, sharing, adaptation, distribution and reproduction 1186/​2046-​4053-4-1
in any medium or format, as long as you give appropriate credit to the 12. Karinkanta S, Kannus P, Uusi-Rasi K, Heinonen A, Sievanen
original author(s) and the source, provide a link to the Creative Com- H (2015) Combined resistance and balance-jumping exercise
mons licence, and indicate if changes were made. The images or other reduces older women’s injurious falls and fractures: 5-year
third party material in this article are included in the article's Creative follow-up study. Age Ageing 44:784–789. https://​doi.​org/​10.​
Commons licence, unless indicated otherwise in a credit line to the 1093/​ageing/​afv064
material. If material is not included in the article's Creative Commons 13 Korpelainen R, Keinanen-Kiukaanniemi S, Nieminen P, Heik-
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Authors and Affiliations

Isabelle Hoffmann1,2 · Matthias Kohl2,3,4 · Simon von Stengel1,2,4 · Franz Jakob2,4,5 · Katharina Kerschan‑Schindl2,4,6 ·
Uwe Lange2,4,7 · Stefan Peters2,4,8 · Daniel Schoene1,2,4 · Cornel Sieber2,4,9 · Friederike Thomasius2,4,10 ·
Heike A. Bischoff‑Ferrari2,11,12 · Michael Uder2,4,13 · Wolfgang Kemmler1,2,4,13

1 8
Institute of Medical Physics, Friedrich-Alexander University German Association for Health-Related Fitness and Exercise
Erlangen-Nürnberg, Henkestrasse 91, 91052 Erlangen, Therapy (DVGS E.V.), Hürth‑Efferen, Germany
Germany 9
European Geriatric Medicine Society (EuGMS), Institute
2
Department of Aging Medicine, University Hospital Zurich for Biomedicine of Aging, FAU Erlangen-Nürnberg,
and City Hospital Zurich, Zurich, Switzerland Erlangen, Germany
3 10
Department of Medicine and Life Sciences, University Osteology Umbrella Association Austria, Germany,
of Furtwangen, Schwenningen, Germany Switzerland
4 11
Institute of Radiology, University Hospital Erlangen, Department of Geriatrics and Aging Research, University
Erlangen, Germany Hospital of Zurich, City Hospital of Zurich-Waid
5 and University of Zurich, Zurich, Switzerland
Bernhard‑Heine‑Center Movement Science, University
12
of Würzburg, Würzburg, Germany Centre On Aging and Mobility, University of Zurich, Zurich,
6 Switzerland
Austrian Society for Bone and Mineral Research, Vienna,
13
Austria Research and Writing Group On Austria/Germany/Suisse
7 S3 Guideline “Exercise and Fracture Prevention” (Bone
German Society for Physical and Rehabilitative Medicine,
Division), Erlangen, Germany
Ulm, Germany

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