Osteoporosis and Sarcopenia xxx (xxxx) xxx

Contents lists available at ScienceDirect

Osteoporosis and Sarcopenia

journal homepage: http://www.elsevier.com/locate/afos

Review article

Non-pharmacological interventions for osteoporosis treatment:

Systematic review of clinical practice guidelines
Roberto Coronado-Zarco a, *, Andrea Olascoaga-Go
mez de Leo

n b, Araceli García-Lara c,
Jimena Quinzan
s Nava-Bringas b,
~ os-Fresnedo d, Tania Ine
Salvador Israel Macías-Herna
ndez b

a
n “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

Directorate of Rehabilitation Medicine, Instituto Nacional de Rehabilitacio
b
n “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico
Spine Rehabilitation and Osteoporosis Clinic, Instituto Nacional de Rehabilitacio
c
Audiology, Hospital Infantil de M
exico “Federico Go
mez”, Mexico City, Mexico
d
n “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico
Neurologic Rehabilitation, Instituto Nacional de Rehabilitacio

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: The aim of this study was to perform a systematic review of clinical practice guidelines to
Received 13 May 2019 identify nonpharmacologic recommendations for osteoporosis treatment.
Received in revised form Methods: A systematic review of literature following PRISMA (Preferred Reporting Items for Systematic
18 June 2019
Reviews and Meta-Analyses)-statement methodology for clinical practice guidelines was conducted;
Accepted 11 September 2019
Available online xxx
PROSPERO CRD42019138548. Assessment of selected clinical practice guidelines with the AGREE
(Appraisal of Guidelines for Research & Evaluation)-II methodological quality instrument was performed,
and those graded over 60 points were selected for recommendations extraction and evidence analysis.
Keywords:
Osteoporosis
Results: Only 6 clinical practice guidelines fulfilled criteria, 69 nonpharmacological recommendations
Nonpharmacologic treatment were extracted: 13 from American Association of Clinical Endocrinologists and American College of
Clinical practice guideline Endocrinology guideline, 16 from Malaysian Osteoporosis Society guideline, 15 from the Ministry of
Recommendations Health in Mexico guideline, 14 from Royal Australian College of General Practitioners guideline, 7 from
Sociedad Espan ~ ola de Investigacio


n Osea y del Metabolismo Mineral guideline, and 7 from National
Osteoporosis Guideline Group guideline. Percentage by theme showed that the highest number of rec-
ommendations were 12 (17.1%) for vitamin D, 11 (15.7%) for a combination of calcium and vitamin D, and
11 (15.7%) for exercise.
Conclusions: These recommendations address integrating interventions to modify lifestyle, mainly cal-
cium and vitamin D intake, and exercise. Other recommendations include maintaining adequate protein
intake, identification and treatment of risk factors for falls, and limiting the consumption of coffee,
alcohol and tobacco. Considerations on prescription must be taken.
© 2019 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction through recommendations that synthetize the best available evi-

dence [3].
Given the overwhelming amount of information currently A frequent problem that the clinician faces is selecting guide-
published, at least 75 trials and 11 systematic reviews every day lines with adequate methodology. The quality of a clinical guideline
[1,2], it is difficult for the clinician to keep up with evidence pro- is defined as “the confidence that potential biases in the develop-
duction to integrate it in his daily practice. Clinical practice ment of a guide have been adequately managed and that the rec-
guidelines (CPG) are intended to assist clinicians in decision making ommendations have internal and external validity, and are feasible
for clinical practice” [4,5]. In Mexico, Centro Nacional de Excelencia
Tecnolo
gica en Salud (National Center of Health Technology
Excellence, CENETEC) develops CPGs; those available for the
* Corresponding author. Directorate of Rehabilitation Medicine, Calz. Me
xico-
treatment of osteoporosis are not updated (https://cenetec-
Xochimilco 289, Mexico City, 14389, Mexico.
E-mail address: [email protected] (R. Coronado-Zarco). difusio
n.com/GPC-sns/).
Peer review under responsibility of The Korean Society of Osteoporosis. The goal of osteoporosis treatment is the prevention of fragility

https://doi.org/10.1016/j.afos.2019.09.005
2405-5255/© 2019 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
2 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx

fracture [6]. This should be achieved through a multidisciplinary 2.3. Synthesis of recommendations
treatment that includes pharmacological and nonpharmacological
interventions. There is lack of knowledge and implementation of Analysis was performed using a descriptive textual synthesis
recommendations for nonpharmacological treatment. directed to scope, context and consistency. Recommendations were
The aim of this study was to perform a systematic review of CPG selected based on the proposed question. Interventions were cate-
for osteoporosis with high methodological quality, to identify gorized by theme (e.g., calcium, vitamin D, exercise). Synthesis of
nonpharmacological interventions and favor its implementation in recommendations was done by a panel of reviewers in a consensus
daily practice in Mexico. process using RAND-UCLA method. It grades appropriateness in a 9-
point scale based on assessment of benefit/harm risk assessment,
2. Methods where 9 represents that benefits overcome harms and 1 represents
that harms overcome benefits. Each panelist was asked to assess and
The present document is derived from an osteoporosis CPG grade in individual way the extracted recommendations. Assess-
adaptation protocol, through the ADAPTE process by the Guidelines ment was reviewed and synthetized by median calculation. Only
International Network [7] and considering GRADE-ADOLOPMENT recommendations with a median between 7 and 9 were considered
model [8]. Guideline adaptation is the systematic approach to the appropriate according to the RAND-UCLA method; discussion was
endorsement and/or modification of a guideline(s) produced in one then performed to select and synthetize recommendations.
cultural and organizational setting for application in a different
context. For this purpose, we developed a systematic review of CPG
3. Results
for diagnosis and treatment of osteoporosis. The proposed question
to assess nonpharmacological interventions through the ADAPTE
Two-hundred forty-one references were identified through
process was: which nonpharmacological treatments should be
databases search, and 208 were excluded that were not clinical
considered in patients with osteoporosis?
guidelines (e.g., guidance, reviews of literature, randomized
controlled trials). Of the 33 selected guidelines, 21 were eliminated
2.1. Identification and selection of guidelines
as they were classified as S1 and S2 by the AWMF criteria [11e31].
Of the remaining 12 [32e43], 6 were eliminated after AGREE-II
A systematic literature review aimed to identify CPG for the
assessment (Fig. 1, Table 1). Intraclass correlation coefficient is
treatment of osteoporosis was conducted (PROSPERO
shown in Table 2.
CRD42019138548). The language was limited to English and
Characteristics of the selected guidelines were documented,
Spanish; the search strategy was designed using: MeSH (medical
including the classification used for level of evidence and grade of
subject headings) terms (osteoporosis, guideline, and treatment),
recommendation (Table 3). The CENETEC guideline [32] was
Boolean operators and advanced search in five different databases
included even though the evidence levels were not stated, since
(PubMed, PEDro, Ovid, Embase, and ScienceDirect), publication
they had already been extracted from the original guidelines.
dates from 2012 to June 18th, 2019 (see Appendix). Three reviewers
From the 6 selected clinical guidelines, 69 nonpharmacological
(RCZ, AGL, AOGL) analyzed abstracts and retrieved full-text of
recommendations were extracted: 13 from AACE/ACE guideline
documents identified as CPG. As this is an adaptation process, we
[33], 16 from Malaysian Osteoporosis Society guideline [34], 15
decided to include the last update of CPG from CENETEC since it is
from CENETEC guideline [32], 14 from RACGP guideline [37], 7 from
published by the Mexican health system, even it is from 2009.
SEIOMM guideline [39], and 7 from NOGG guideline [41]. Only one
Classification of CPG was performed by two reviewers (RCZ,
recommendation was modified by consensus. Percentage by theme
AOGL) based on the published methodology of each CPG applying
showed that the highest number of recommendations were for
the following categorization of the Association of the Scientific
vitamin D with 12 (17.1%), exercise with 11 (17.1%), and a combi-
Medical Societies in Germany (AWMF) [9,10]: S1 expert recom-
nation of calcium and vitamin D with 11 (15.7%) (Table 4).
mendations contain treatment recommendations developed by
informal consensus of a group of experts, S2 guidelines are created
by formal consensus-finding and/or formal search for evidence, and
S3 guidelines contain all of the elements of systematic develop-
ment: representative committee, systematic review and synthesis
of the evidence, structured consensus process. Only S3 CPG were
included.

2.2. Clinical practice guidelines assessment

AGREE-II methodological quality assessment was performed by

three independent reviewers for each guideline; agreement reli-
ability was done through intraclass correlation coefficient, which
was considered over 0.6 as substantial agreement. Platform https://
www.agreetrust.org/ was used, it includes 23 items rated from 1
(strongly disagree) to 7 (strongly agree) each one. All items are
grouped in 6 domains: scope and purpose, stakeholder involve-
ment, rigor of development, clarity of presentation, applicability
and editorial independence. An overall guideline assessment and
recommendations for use are included: yes, yes with modifications,
no. CPG graded 60 points or more in the overall guideline assess-
ment were selected for recommendations extraction. All these Fig. 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
recommendations of non-pharmacological interventions were flow diagram of guidelines selection process. AGREE, Appraisal of Guidelines for
included for analysis, evidence level and recommendation strength. Research & Evaluation.

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx 3

Table 1
AGREE-II assessment of clinical guidelines.

Domain Description Guidelines

AACE Malaysian Philipinnes CENETEC CENETEC CENETEC RACGP Rheumatology SEIOMM NOGG NOGG AMMOM
[33] [34] [43] [35] [32] [36] [37] [38] [39] [40] [41] [42]

I Source and purpose 81 94 91 22 94 59 91 19 22 24 67 85

II Stakeholder involvement 50 69 44 19 61 52 57 20 69 22 74 59
III Rigour of development 74 60 61 22 67 49 69 27 69 24 63 51
IV Clarity of presentation 80 85 80 22 72 65 93 37 70 20 85 43
V Applicability 24 88 17 19 25 19 47 22 24 21 61 28
VI Editorial independence 67 58 19 22 39 61 33 19 44 19 83 11
Overall guideline 67 61 50 22 72 44 67 33 61 22 78 50
assessment

Would you recommend this guide for use? (3 ¼ yes; 2 ¼ yes with modifications; 1 ¼ no)
Reviewer 1 2 2 1 2 2 1 2 2 2 2 2 2
Reviewer 2 2 2 2 1 2 2 2 1 2 1 2 2
Reviewer 3 2 2 2 1 2 2 2 1 2 1 2 2

gica en
AGREE, Appraisal of Guidelines for Research & Evaluation; AACE, American Association of Clinical Endocrinologists; CENETEC, Centro Nacional de Excelencia Tecnolo
~ ola de Investigacio
Salud; RACGP, Royal Australian College of General Practitioners; SEIOMM, Sociedad Espan


n Osea y del Metabolismo Mineral; NOGG, National Osteoporosis
Guideline Group; AMMOM, Asociaci o
n Mexicana del Metabolismo Oseo
y Mineral.

Table 2 R2. The use of protein supplements in patients with hip fracture
Reliability assessment: intraclass correlation coefficient (ICC). minimizes bone loss, decreases the risk of infection, de-
CPG Cronbach alpha ICCa CI creases the length of hospital stay and increases functional
AACE [33] 0.775 0.780 0.56e0.89
recovery. Recommended protein intake is 1.2 g/kg daily.
Malaysian [34] 0.765 0.760 0.53e0.89 Modified by consensus from CENETEC guide [33].
CENETEC [32] 0.769 0.685 0.33e0.86 R3. Within the population-based strategies, lifestyle modifica-
RACGP [37] 0.752 0.753 0.52e0.88 tions are recommended to achieve an adequate intake of
SEIOMM [39] 0.749 0.674 0.33e0.85
calcium and sufficient intake of vitamin D (diet, sun expo-
NOGG [41] 0.648 0.637 0.30e0.83
sure) [39,41].
CPG, Clinical practice guideline (N ¼ 3 reviewers); CI, confidence interval; AACE,
R4. The desirable blood levels of vitamin D are 30e50 ng/mL. In
American Association of Clinical Endocrinologists; CENETEC, Centro Nacional de
Excelencia Tecnolo
gica en Salud; RACGP, Royal Australian College of General Prac- case of requiring supplementation, as low blood levels or
titioners; SEIOMM, Sociedad Espan ~ ola de Investigacio


n Osea y del Metabolismo patients with risk factors for low levels, a minimum dose of
Mineral; NOGG, National Osteoporosis Guideline Group. 400 IU is recommended [33]. In patients with greater risk of
a
F test: p ¼ 0.001. deficiency, such as the elderly and the chronically ill, doses
between 800 and 2000 IU are recommended [32].
R5. The recommended calcium intake is 1000e1200 mg daily,
3.1. Synthesis of recommendations of CPGs for practitioner
preferably through nutritional intake. If the diet does not
(implications for rehabilitation)
contain enough, supplementation is required without
exceeding 1200 mg daily. To favor its absorption, it is not
R1. Maintenance of an adequate protein intake is important for
recommended to exceed 500e600 mg per dose
the preservation of musculoskeletal function in post-
[32e34,39,41].
menopausal women and men over 50 years of age
R6. Calcium supplementation is not recommended in older, non-
[33,34,37,41].
institutionalized adults [37].

Table 3
General information of selected guidelines.

Year of Name Organisation Levels of evidence grading system Recommendations grading system
publication

2016 Clinical practice guidelines for the diagnosis and AACE/ACE 2010 Mapping Evidence Levels to 2004 AACE Criteria for Grading
treatment of postmenopausal osteoporosis Recommended Grading Recommendations
2012 Clinical guidance on Management of Malaysian 1999 National Guidelines 2001 Modified SIGN
Osteoporosis Osteoporosis Clearinghouse
Society
2009 Guía de pr
actica clínica para el CENETEC The classification criteria for evidence level and recommendations grading were
diagno
stico y tratamiento de la osteoporosis en based on the original CPG: e.g., Shekelle et al.; US Preventive Services Tasks Force;
el adulto SIGN 2003; Technology assessment report 2000; ICSI Health Care Guidelines
Diagnosis and Treatment of Osteoporosis 2006.
2017 Osteoporosis prevention, diagnosis and RACGP and OA 2009 Adapted from National Health and Medical Research Council
management in postmenopausal women and
men over 50 years of age
2008 Guías de pr
actica clínica en la osteoporosis SEIOMM Oxford Center for Evidence Based Medicine
(update 2014) posmenop
ausica, glucocorticoidea y del varo
n
2017 Clinical guideline for the prevention and NOGG 2017 National Osteoporosis Guideline Development Group
treatment of osteoporosis

AACE/ACE, American Association of Clinical Endocrinologists/American College of Endocrinology; CENETEC, Centro Nacional de Excelencia Tecnolo
gica en Salud; RACGP/OA,
Royal Australian College of General Practitioners/Osteoporosis Australia; SEIOMM, Sociedad Espan ~ ola de Investigacio


n Osea y del Metabolismo Mineral; NOGG, National
Osteoporosis Guideline Group; SIGN, Scottish Intercollegiate Guidelines Network; CPG, clinical practice guidelines; ICSI, Institute for Clinical Systems Improvement.

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
4 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx

Table 4
Synthesis of number of recommendations with level of evidence and strength of recommendations, according to each topic, and based on grading systems mentioned in
Table 3.

Theme and guideline recommendation category AACE [33] Malaysian [34] CENETEC [32] RACGP [37] SEIOMM [39] NOGG [41]

NR LE and/or SR NR LE and/or SR NR LE and/or SR NR LE and/or SR NR LE and/or SR NR LE and/or SR

reported reported reported reported reported reported

Protein intake 2 I 3 IIb; B III; B 1 C 1 Ib

IV IV; C
Calcium 1 II; B 3 Ia; A 1 A 1 y 1 Ia; B
IIa; B
Ia
Vitamin D 4 I; A 4 Ia; A 2 A 1 y 1 Ia; A
II; B IV A
III; B Ia; A
IV; C IIa
Combination of calcium and vitamin D 3 Ia 3 A 2 C 2 Ia,Ib, 1 B
Ia A C IIb; B
Ib B
Vitamin K 1 1; B
Other supplements (magnesium, copper, 1 D
zinc, phosphorus, manganese, iron)
Hip protectors 1 I; B 1 C 1 Ia
Caffeine 2 III; B 2 II; B
III yy
Smoking 1 II; B 1 IIa; B 1 yy 1 C 1 y
Alcohol 1 II; B 1 IIa; B 1 yy 1 C
Physical therapy 1 I; A
Exercise 1 II; B 1 IV; C 3 B 5 B 1 y 1 Ia; B
B C
B A
A
A
Risk falls 1 I; A 2 A 1 y 1 A
A
Education 1 D

AACE, American Association of Clinical Endocrinologists; CENETEC, Centro Nacional de Excelencia Tecnolo
gica en Salud; RACGP, Royal Australian College of General Practi-
tioners; SEIOMM, Sociedad Espan ~ ola de Investigacio


n Osea y del Metabolismo Mineral; NOGG, National Osteoporosis Guideline Group; NR, number of recommendations; LE,
level of evidence; SR, strength of recommendations.
ySEIOMM integrates one recommendation including calcium, vitamin D, smoking, exercise and risk falls. yyCENETEC integrates one recommendation including caffeine,
smoking and alcohol.

R7. Supplementation with vitamin K, magnesium, cooper, zinc, 4. Discussion

phosphorus, iron, or essential fat acids is not recommended
for the prevention or treatment of osteoporosis [32]. The adaptation of a clinical practice guide is an eclectic process
R8. Reducing the intake of caffeine is recommended by limiting that aims to make recommendations, in the form of syncretic
the consumption of no more than 4 cups of coffee per day postulates based on the best and most current evidence available,
[32,34]. giving rise to a true practice based on evidence considering the
R9. Smoking cessation is recommended [32e34,37,39]. contextual situation.
R10. It is recommended to limit the consumption of alcohol to no According to the AGREE methodology, the selection criterion of
more than 2 units per day [32e34,37]. clinical practice guidelines was based solely on the overall rating.
R11. A validated multifactorial assessment of fall risk that evalu- However, it is important to note that this rating is integrated by the
ates the history of falls and risk of fragility fracture is rec- appraiser’s global appreciation of the guide, without considering
ommended in patients over 75 years of age, to decide on numerical rating of each domain.
whom interventions are indicated [33,37,39,41]. Another section of the AGREE method includes the appraiser’s
R12. To reduce the risk of fragility fracture through the prevention recommendations for the usage of each guide: recommended,
of falls, exercise with weight, balance and resistance load is recommended with modifications, not recommended; but these
recommended, to improve mobility, strength and physical results are not considered in the overall rating neither included in
performance [33,37,39,41]. Special attention must be taken the manual of the instrument. It is necessary to consider that all
in patients with high risk of fragility fracture within in- the reviewers recommended the use of the selected guides with
stitutions, through supervision of therapy (e.g., physical modifications, and of the non-selected guides some were recom-
therapy) [33]. mended for their use. Furthermore, based on the AGREE method
R13. The use of hip protectors is recommended for institutional- these guides were not selected for extraction of recommendation.
ized patients with a high risk of falls [34,37,41]. CPG concentrate recommendations on pharmacological in-
R14. Provide postmenopausal women and men over 50 years with terventions. And when considered non-pharmacological in-
risk or diagnosis of osteoporosis access to education, psy- terventions, they provide limited information through
chosocial support and encourage them to seek support from recommendations for these interventions. Reviewing the source of
appropriate sources according to individual needs [33]. evidence used in the CPGs, we found that the majority of articles
were published in past decades, and it is worth mentioning that

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx 5

there is more recent evidence, and some recommendations may consideration, as there are differences in cost, absorption mecha-
have implications in clinical practice. Therefore, we took on the task nisms and associated risks.
of carrying out a review of the current literature of each of the Calcium citrate is the most expensive presentation, its absorp-
recommendations extracted, which we suggest to consider. tion is not affected by concomitant food intake. It produces a lower
Considerations of recommendations based on literature: saturation of calcium oxalate compared to calcium carbonate sup-
plements, and for this reason it may be indicated in the presence of
Recommendation 1. Maintenance of an adequate protein nephrolithiasis [52].
intake is important for the preservation of musculoskeletal One of the most important pharmacological interaction that
function in postmenopausal woman and man over 50 years of need to be considered is with protein pump inhibitors (PPI).
age. Omeprazole 20 mg for 7 days significantly decreases the absorption
Recommendation 2. The use of protein supplements in patients of calcium carbonate under fasting conditions with elevated pH,
with hip fracture minimizes bone loss, decreases the risk of although the effect of concomitant food intake is unknown [53].
infection, decreases the length of hospital stay and increases Potential mechanisms underlying the association of PPI and the risk
functional recovery. Recommended protein intake is 1.2 g/kg of fragility fracture may be related to effects of chronic acid sup-
daily. pression on calcium metabolism [54]:

Malnutrition in elderly population is frequent, prevalence range (1) Chronic hypergastrinemia induced by PPI therapy may lead
from 14% to 40% in elderly subjects [44]. Protein supplementation to parathyroid hyperplasia primary hyperparathyroidism,
in institutionalized patients with recent hip fracture improves resulting in increased loss of calcium from the bone trough
subsequent clinical course by diminishing length of hospital stay parathormone (PTH) elevation.
and infection rate [45]. In general population, protein intake di- (2) Profound gastric acid suppression may reduce the bioavail-
minishes bone mineral loss and increases muscle strength, prob- ability of calcium for intestinal absorption, which may lead to
ably by improving insulin-like growth factor-1 levels [46]. secondary hyperparathyroidism, and increased PTH.
The extracted recommendation on protein intake is 0.8 g/kg/
day. There is evidence that suggest that the recommended intake The form of supplementation must be ionized. Under physio-
protein for general elderly population is 1e1.2 g/kg/day, and is most logical conditions calcium is absorbed by 90% in the small intestine
effective on muscle and bone mass when combined with exercise (duodenum); one of the main determinants of this process is the
[47]. For this purpose, the consensus considered to modify the concentration of calcitriol (1,25-dihydroxyvitamin D3). Any condi-
original recommendation 0.8 g/kg/day because this is based on the tion that decreases ionized serum calcium triggers PTH increase.
Food and Nutrition Board of recommended dietary allowance, but it Ingested calcium requires hydrochloric acid to become Ca2þ. The
reflects the lowest end of the acceptable macronutrient distribution consumption of fasting calcium and patients with decreased gastric
range [48]. acid secretion have reduced absorption [54].
Calcium carbonate is poorly soluble, it needs to be converted to
Recommendation 3. Within the population-based strategies, calcium chloride in the presence of hydrochloric acid. Calcium
lifestyle modifications are suggested to achieve an adequate citrate, calcium lactate and calcium gluconate are more ionizable
intake of calcium and sufficient intake of vitamin D (diet, sun and soluble in the presence of a neutral pH. In patients with
exposure). achlorhydria, calcium citrate is absorbed 10 times more than cal-
Recommendation 4. The desirable blood levels of vitamin D are cium carbonate [54].
30e50 ng/mL. In case of requiring supplementation, a minimum Calcium salts are linked to abdominal distension, because they
dose of 400 IU is recommended. In patients with greater risk of react with hydrochloric acid and produces carbonate dioxide
deficiency, such as the elderly and the chronically ill, doses be- release that clinically presents as meteorism and flatulence. Cal-
tween 800 and 2000 IU are recommended. cium citrate does not produce carbon dioxide, so it has not been
Recommendation 5. The recommended calcium intake is linked to these phenomena. There is controversy about the possible
1000e1200 mg daily, preferably through nutritional intake. If it cardiovascular risks due to calcium supplementation. Recent evi-
is not completed, supplementation is required without dence has linked calcium supplements with increased risk of cor-
exceeding this amount. To favor its absorption, it is not recom- onary artery calcification [55].
mended to exceed 500e600 mg per dose. A general recommendation for daily calcium requirements is
Recommendation 6. Calcium supplementation is not recom- that, when possible, it should be achieved through an adequate
mended in older, noninstitutionalized adults. intake of calcium enriched foods [56,57].
Recommendation 7. Supplementation with vitamin K, magne- Recommendations issued by the US Preventive Services Task
sium, cooper, zinc, phosphorus, iron or essential fat acids is not Force (USPSTF) establish that there is not enough evidence to
recommended for the prevention or treatment of osteoporosis. evaluate the balance between the benefits and the risks of vitamin
D and calcium supplementation, alone or in combination, for the
Apparently, calcium supplementation is not so innocuous. Cal- prevention of fragility fracture in subjects in the community. The
cium prescription should be based on a detailed analysis of calcium current evidence is insufficient to assess the balance between the
intake. The excessive calcium intake may lead to hypercalcemia. benefits and risks of daily supplementation with doses greater than
Patients who have an adequate calcium intake through diet have a 400 UI of vitamin D or greater than 1000 mg of calcium in the
reduced risk of kidney stone formation, in contrast with calcium primary prevention of fragility fracture in postmenopausal women
supplementation consumers, who are at a higher risk. On the other living in community. Supplementation with 400 IU or less of
hand, patients with type 2 diabetes are more prone to uric acid vitamin D and 1000 mg or less of calcium is not recommended for
stone development [49]. the primary prevention of fragility fracture in postmenopausal
Similarly, hypervitaminosis D is a rare cause of hypercalcemia. women living in the community (Recommendation D). These rec-
After long term (7 years) vitamin D supplementation, an increase of ommendations do not apply to people with history of fragility
17% for kidney stone risk formation was detected [50,51]. fracture due to osteoporosis, high risk of falls or for the diagnosis of
When prescribing calcium, the type of salt must be taken in osteoporosis or vitamin D deficiency [57]. Our position is that the

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
6 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx

intake of calcium and levels of vitamin D and calcium should be Alcohol intake is associated with increased fracture risk, with
assessed to determine the need for supplementation. multifactorial mechanism including a negative effect on bone for-
There is lack of evidence on the relation between vitamin K, mation, predisposition to falls, calcium deficiency and chronic liver
magnesium, cooper, zinc, phosphorus, iron or essential fatty acids disease, which causes vitamin D deficiency [86].
and osteoporosis; only considered by one CPG [32] in which sup- Although there is controversial evidence about alcohol con-
plementation was not recommended. sumption and its effects on bone, a recent study [87] pointed out
that light consumption (2e3 times per week and from 1 to 2 or 5 to
Recommendation 8. It is recommended to reduce the intake of 6 drinks per event) is related to a higher concentration of BMD
caffeine by limiting the consumption of no more than 4 cups of (total femur, femoral neck, femoral trochanter, and intertrochan-
coffee per day. teric region) compared to nondrinkers and heavy-drinkers. The
latter showed a 1.7 times higher risk than light drinkers. The same
Evidence of observational studies has shown an association author indicated that the interpretation of these results should be
between caffeinated beverages consumption and fragility fracture taken with caution, due to the complex nature of associations that
[58]. Caffeine decreases intestinal calcium absorption and increases may exist among alcohol consumption, BMD and socioeconomic
urinary calcium excretion. Although this effect could be related to conditions.
the replacement of milk in the diet.
The effect of different drinks containing caffeine has been Recommendation 11. A validated multifactorial assessment of
implicated as a cause of osteoporosis and fragility fracture [59]. Due fall risk that evaluates the history of falls and risk of fragility
to the information of observational studies in favor and against this fracture is recommended in patients over 75 years of age, to
association, there is controversy [60]. Some studies have suggested decide on whom interventions are indicated.
that the effect of coffee on bone health may be mediated by Recommendation 12. To reduce the risk of fragility fracture
different mechanisms: deleterious effect on osteoblasts [61,62], through the prevention of falls, exercise with weight, balance
increased urinary calcium excretion [63e65], decrease in the effi- and resistance load is recommended, to improve mobility,
ciency of intestinal absorption [66], osteoblasts apoptosis [61] and strength and physical performance. Special attention must be
low calcium intake in coffee drinkers [67,68]. taken in patients with high risk of fragility fracture within in-
The cytotoxicity of caffeine has been linked to apoptosis [61,69]. stitutions, through supervision in the execution (e.g., physical
Caspases [70] and Bcl-2 family [71] play an important role in therapy).
apoptosis, they regulate mitochondrial membrane potential
changes and the release of cytochrome C by modulating the Evidence for exercise as osteogenic therapy is not sufficient. The
permeability of the outer mitochondrial membrane. benefits of exercise are related to reduction of fall risk. There are
Heavy caffeine intake increases the urinary excretion of calcium, many conditions that shall be taken in consideration when pre-
whereas moderate coffee consumption (1e2 cups per day) does not scribing exercise for osteoporosis, like comorbidities [88]. Besides,
have a significant impact on calcium imbalance in postmenopausal there is little information on CPG related to prescription of exercise
women [64]. by means of type, intensity, duration and frequency.
At the same time, recent evidence suggests that coffee con- Most guidelines recommend the analysis of risk of falls, but its
sumption can help reduce the risk of several diseases: type 2 dia- performance is not detailed. Exercise decreases risk of falls by
betes, Parkinson disease, Alzheimer disease, cardiovascular disease improving resistance, force and balance, but there is controversy on
and cancer [65]. its evidence. A recent Cochrane systematic review concluded that
Coffee may exert beneficial effects on bone health due to its high even there is little or no effect on other fall-related outcomes,
polyphenols composition, the impact may be especially prominent multifactorial and multicomponent interventions, usually
in men, who are resistant to caffeine-induced bone loss [72,73]. including exercise, may reduce the rate and risk of falls compared
Recent evidence supports this assumption on younger [74] and with usual care or attention control [89].
older [75] males. Recommendations for physical therapy include exercise training
in resistance and balance after hip fracture to improve mobility,
Recommendation 9. Smoking cessation is recommended. strength and physical performance. There is limited evidence for its
benefits after vertebral and non-hip fragility fracture [37].
There is evidence that tobacco smoking increases fragility frac-
ture risk [76] and that current active smokers have higher risk than Recommendation 13. The use of hip protectors is recom-
previous smokers [77]. But, there is a lack of evidence to determine mended for institutionalized patients with a high risk of falls.
whether smoking cessation will reduce fracture risk, and no clear
mechanisms have been proposed. There is limited evidence that allows the recommendation for
Mechanisms linked to bone loss due to tobacco: decreases in- hip protectors other than institutionalized patients. However poor
testinal calcium absorption [78], decreases body weight in women acceptance and adherence of patients it’s a barrier. As most treat-
[78e80], it can anticipate menopause age [81], promotes alter- ments for osteoporosis compliance plays a key role [37,90].
ations of the blood supply of the femoral head [82], decreases
vitamin D levels [83] with stronger association in decreased spinal Recommendation 14. Provide postmenopausal women and
bone mineral density (BMD) and affects estrogenic metabolism in men over 50 years with risk or diagnosis of osteoporosis access
women [84] and androgenic in men [85]. to education, psychosocial support and encourage them to seek
Even though these mechanisms have been linked to osteopo- support from appropriate sources according to individual needs.
rosis, it is difficult to analyze the impact of cigarette smoking
because there are indirect effects involved, such as socioeconomic, Education must be focus on awareness about the disease pro-
physical and nutritional factors. cess, prevention of fragility fracture, pain management, rehabili-
tation techniques and fall prevention and the importance of
Recommendation 10. It is recommended to limit the con- therapy compliance. There is little information on how to achieve
sumption of alcohol to no more than 2 units per day. and assess conduct modifications to ensure adequate therapy

Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
 R. Coronado-Zarco et al. / Osteoporosis and Sarcopenia xxx (xxxx) xxx 7

adherence and compliance. 2013;8(12):e82915. https://doi.org/10.1371/journal.pone.0082915.

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practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005
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Please cite this article as: Coronado-Zarco R et al., Non-pharmacological interventions for osteoporosis treatment: Systematic review of clinical
practice guidelines, Osteoporosis and Sarcopenia, https://doi.org/10.1016/j.afos.2019.09.005