Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club

As many other chronic conditions, osteoporosis (OP) has a multifactorial origin. If it is admitted that at least 46–62% of the variance in bone mineral density (BMD) depend of genetic factors, consequently around 38–54% of the variance of BMD can be modified by environmental factors, in which nutrition plays a large part [11, 12]. Regarding the skeleton, nutrition could theoretically have a direct and indirect role: firstly, to maximize bone strength during growth through the amelioration of the peak bone mass, by improving both the proteic compartment of bone and the mineralization, and by decreasing the rate of bone loss with ageing; secondly, to maintain the muscle strength by restraining sarcopenia in elderly. Physical activity has also a role, either isolated or in combination with nutrition. Increase in physical activity and calcium intake can indeed maximize bone gain chiefly at loaded sites [13, 14]. The combined effect of nutrition and exercise has been less studied for other nutriments. Moreover, during growth, an interaction between environment, hormonal factors, nutrition, ethnicity, sex, and genetics probably exists. Even complicating more the study of the relationship between nutrition and BMD, studies have shown a positive link between maternal nutrition, body build, and fat stores during pregnancy with whole body bone mineral content in children at the age of 9, and even with adult bone mass [15]. A higher whole body peak bone mass has been associated with breast-feeding, suggesting the presence of other factors than nutritive factors in human milk [16]. These direct and indirect incentives of nutrition on BMD, bone structure, and bone metabolism, as well as the weak correlation between the nutritional intakes and their quantitative evaluation (e.g. food frequency questionnaires; r = 0.31–0.71) might only partly reflect the long-term influence of feeding on bone. This could explain the difficulty in determining precisely the role of the nutritional intakes [17]. On the top of these difficulties, it should be remembered that the influence on the skeleton of some nutriments such as calcium is not linear, but has a threshold effect probably variable across the age groups [18]: lower than the threshold, there is some risk of bone loss, around the threshold, bone maintenance is observed, and above the threshold, there is no further additive effect [18]. The role of calcium and vitamin D in the treatment of OP has been recently reviewed in the last BBC consensus [3]. Therefore their role will not be further discussed. Suffice here to remember that the antifracture efficacy is better for a daily intake of 1,000–1,200 mg calcium and 800–880 IU vitamin D [19].

Excesses in sodium intake have a negative impact on calcium balance by increasing the urinary calcium excretion. There is, however, an interindividual differences in salt sensitivity. Obligatory urinary calcium losses are correlated with urinary sodium excretion [20]. For every 100 mmol of sodium excreted, approximately 1 mmol loss of urinary calcium is observed [20]. It has been suggested, however, that enough calcium in the diet could overcome the salt deleterious effect. There could be 2-fold differences in sodium-induced calciuria with low and high calcium intakes. In a recent study, as compared with a low salt diet (3.9 g/day), a high salt intake (11.2 g/day), corresponding to upper intakes in postmenopausal women on a Western-style diet provoked a significant increase in urinary calcium excretion (+36%). The negative bone calcium balance was not counteracted by a high calcium diet (1,284 mg/day). Paradoxically, the negative bone calcium balance induced by both high and low salt diets was less marked with a low calcium intake. There was a significant increase in the levels of parathyroid hormone (+11.4%) and of urinary N-telopeptide (+19%) in response to the high sodium diet [21].

In previous studies such as the Framingham study, in a 12-year follow-up, the risk of hip fracture over each 2-year period was found significantly increased by the consumption of ≥2.5 units of caffeine per day (one cup of coffee = one unit of caffeine, and one cup of tea = 0.5 unit of caffeine) [22]. There is a theoretical explanation to the fragilization of bone by caffeine intake: caffeine increases urinary and faecal calcium losses and may provoke a negative calcium balance in presence of a low calcium diet [23]. Caffeine at a dose of 330 mg/day (i.e. four cups (600 ml)) possibly might be associated with a modestly increased risk of osteoporotic fractures (Hazards ratio, 1.20 (95% confidence interval (CI), 1.07–1.35)), compared with a low caffeine intake (<200 mg/day) [24]. However, this deleterious effect of caffeine seems to be offset by increasing calcium intake (by 40 mg calcium for every 177.5 ml serving of caffeine-containing coffee, i.e. ∼1 cup) [25]. This positive calcium effect greatly minimizes a potential role for caffeine in BMD maintenance and bone strength. No study has been done with decaffeinated coffee.

High phosphorus intakes are associated with lower levels of calcium urinary excretion, but a slightly higher intestinal calcium excretion. These opposite effects neutralize themselves and does not seem to negatively impact on calcium balance [26, 27].

The role of protein intake remains controversial in the development of osteoporosis. Excessive protein intake can be responsible for a metabolic increase of acid production and acid renal excretion, with increased calciuria potentially favouring bone loss and hip fracture [26, 28]. Hypercalciuria is not necessarily due to an increase in bone resorption. Intestinal calcium absorption is indeed positively influenced by protein intakes, probably secondary to insulin-like growth factor-1 (IGF-1) production [29, 30]. On the contrary, in postmenopausal women, but also in men, a positive association between protein intakes and BMD has been rather observed [28, 31]. In men and women, a mean loss of BMD of −4.61% and −3.72% was observed in patients with the lowest quartile of protein intake (17–53 g/day), versus a loss of −2.32% and −1.11% in patients with the highest quartile (84–152 g/day) at the femoral neck and spine, respectively [31]. Munger et al. also observed that the risk of hip fracture was not associated with calcium or vitamin D intake, but was negatively related to total protein intake. Proteins of animal and not vegetable origin apparently accounted for this association. The relative risk for hip fracture seemed to decrease paralleling the intake in animal protein [32]. In another study, elderly women consuming less than 66 g protein/d had lower values (1.3–2.2%) of quantitative ultrasound of the heel (broadband attenuation and stiffness measurements) and lower hip BMD (2.5–3.0%) than patients eating more than 87 g protein/day [33]. Contrarily to these positive effects of protein intake on BMD, Sellmeyer et al. showed in a prospective cohort study that a high diet ratio of dietary proteins of animal origin over vegetable protein could induce a higher rate of bone loss at the femoral neck and an increased risk for hip fractures (relative risk = 3.7) in women aged more than 65 years [34]. This apparent deleterious effect of animal protein intake could be counteracted by dietary or supplemental calcium (500 mg as calcium citrate malate and vitamin D (700 IU) per day) [35]. As far as the relationship between fractures and protein intakes were concerned, some contradictory results have been observed for the forearm fracture and hip fractures [36]. A slightly higher risk for forearm fractures was observed in women consuming more than 95 g per day protein as compared with those consuming less than 68 g per day (relative risk = 1.22), whereas no association was found with hip fracture [36]. This discrepancy could find its origin in the fact that people with a higher protein intake have a longer life expectancy possibly accounting for a higher forearm fracture incidence [37]. Calcium intake can also interfere with protein intake, a low dietary calcium potentially blunting the positive effect of high protein intake [31, 35]. However, data from the 1999 to 2002 National Health and Nutrition Examination Survey does not show any association between total calcium intake and risk of fracture in postmenopausal women. An inadequate dietary protein intake in the presence of adequate total calcium intake does not seem to confer any protection against fractures [38]. Once hip fracture has occurred, a 20-g protein supplementation could lead to a lower rate of general complications such as bed-sores, infections, deaths, etc., and allow a shorter stay in the hospital as shown in a study [39]. The observed effect is probably due to a positive influence of dietary proteins on the production of IGF-I [30]. Some studies incriminated vegetarism for increasing bone remodelling and decreasing BMD [40, 41]. The lower BMD observed might not be clinically relevant, no difference in fracture risk between vegetarians and nonvegetarians having been demonstrated in a large study [42]. Vegetarianism should therefore not be considered as a risk factor for osteoporotic fracture. As this issue is that complicated, it seems reasonable to recommend a balanced diet between vegetable and animal proteins until further studies determine the most appropriate regime. Indeed, it is not yet clearly demonstrated that bone resorption induced by vegetables is dependent of acid–base changes in protein intake [43]. Finally, protein might play a role in maintenance of BMD by different mechanisms, e.g. by increasing IGF-1, calcium absorption, and muscle strength and mass, which all could benefit the skeleton [44].

Potassium content, high in fruits and vegetables has a protective effect against urinary calcium loss. However, this positive effect can be completely offset by a low calcium intake or a reduction in intestinal absorption. The best way to preserve the body calcium economy is to encourage the consumption of foods such as dairy products, which are rich in calcium, proteins, phosphorus, and potassium [45].

In postmenopausal women, an increased intake of some minerals and vitamins could prove to be able to decrease bone loss [46]. This favourable effect has been suggested for magnesium, boron (contained in dried-plums), vitamin C, vitamin K, and fluor, but it is not commensurate to the effect of calcium and vitamin D. Mononutrical supplements will frequently be inadequate and preference should go to the use of complete supplements or foods (e.g. dairy products) [45]. These supplements should be potentially useful mostly in late postmenopause and in elderly people [46]. However, their exact role in bone metabolism as compared with calcium/vitamin D supplementation remains to be demonstrated [47, 48].

High-fibre diets (≥30 g/day) could provoke a 20–30% decrease in intestinal calcium absorption [49]. A lowered plasma estradiol level has also been attributed to fibre excess, but the effect on the skeletal integrity has not been clearly settled [50].

Soy isoflavones are natural products structurally and functionally related to 17 beta-estradiol. In vitro and animal studies have suggested that phytoestrogens act on both osteoblasts and osteoclasts through genomic and nongenomic pathways [51]. In a recent meta-analysis including data from 1,240 postmenopausal women, daily ingestion of on average 82 mg soy isoflavones for 6 to 12 months was accompanied by a significant increase in spine BMD (+2.38% (95% CI, 0.93–3.83; p = 0.001)), compared with controls [52]. In a large randomized, placebo-controlled trial, ipriflavone, another soy isoflavone did not prevent bone loss nor affected biochemical markers of bone remodelling in Western Caucasian postmenopausal women. Moreover, lymphocytopenia was observed in a significant number of women [53]. However, several epidemiological studies and clinical trials suggest that some soy isoflavones have beneficial effects on bone turnover markers and bone mechanical strength in postmenopausal women [54]. It is possible that the varying effects of isoflavones on spine BMD across trials might depend on study characteristics, duration of therapeutic intervention (6 versus 12 months), origins of the patients (Asia versus Western countries), race, and baseline BMD (normal BMD, versus osteopenia, or osteoporosis). No significant effect has ever been observed on femoral neck, total hip and trochanter BMD. Further longer studies are necessary, because the role of soy isoflavones in bone economy remains unclear. Their long-term safety is still to be precisely stated. Use of calcium-reinforced soy isoflavones could be considered.

Bone quality in adults mostly depends on the equilibrium in bone remodelling. The latter is influenced by hormonal factors, in connexion with adequate mechanical loading and sufficient intake of macro- and micronutrients. The well known, because better and more extensively studied, elements are calcium, proteins and vitamin D. Diets deficient in one of the above-mentioned nutriments will certainly be at risk of impairing skeleton integrity. However, it is possible that the optimal health of the skeleton requires a good equilibrium between all nutrients. As already mentioned above, it is probable that mononutrient supplementation, as frequently recommended in several diets will not necessarily lead to an adequate bone quality [53].

The main objective of physical exercise in the prevention or treatment of osteoporosis is to reduce fracture incidence. Unfortunately, no large, well-designed controlled trial assessed, so far, the effect of exercise therapy with fracture as an outcome. As a result, exercise interventions for patients with osteoporosis mainly reported the reduction of risk factor for fracture, i.e. a decrease in the propensity to fall and/or an increase in BMD. Because mobility impairments, such as reduced balance and muscle strength, are risk factors for falls and fractures, they have also been used as outcomes in clinical trials [55].

Epidemiological studies have identified a large number of risk factors for osteoporotic fracture. These can be risk factors related to bone strength, i.e. bone density, geometry and/or quality, or factors independent of bone strength, essentially related to risk for falls (one for review). Amongst the identified risk factors only some are potentially modifiable. Such risk factors that can be considered as somehow related to lifestyle are listed in Table 1.

Low body weight or low BMI is a well-recognized risk factor for fracture, whereas overweight and obesity have generally been considered as protective [79, 80]. However, recent evidence tends to challenge this view and suggests that increased adiposity and obesity, which has been associated with higher prevalence of vitamin D insufficiency and in some studies also of secondary hyperparathyroidism [81, 82], can have a negative impact on indices of bone strength and possibly on fracture risk [83‐87]. Albeit the available evidence thus suggests that a lifestyle that helps maintaining a more ideal body weight is beneficial for bone health, presently there is no evidence that interventions aimed at gaining or losing weight in thin and obese persons, respectively, can reduce fracture risk. In fact, weight loss in obese subjects has been associated with increased bone loss [88]. In this context, weight loss following bariatric intestinal bypass surgery, but probably not following gastric banding, has been associated with prolonged elevations of the levels of biochemical markers of bone turnover and with bone loss, also in absence of vitamin D insufficiency or increase of serum PTH [82, 89, 90].

As to more specific lifestyle factors related to diet, the potential adverse skeletal effects of low calcium intake, high sodium intake and excessive caffeine consumption have been addressed in the section on nutrition. The use of carbonated soda drinks and more in particular of colas has been associated with lower bone mass. Besides displacement of more nutrient- and calcium-rich beverages, caffeine, and phosphoric acid content in colas have also been implicated as contributing to the adverse skeletal effects [13, 91].

Excessive alcohol consumption is generally recognized as a secondary cause of osteoporosis and as a risk factor for fracture [79]. Alcohol may interfere with bone metabolism through direct toxic effects on osteoblasts and indirectly through adverse skeletal effects of nutritional deficiencies in calcium, vitamin D, and proteins that are prevalent in heavy drinkers. However, increased fracture risk is explained only for a minor part by increased bone fragility and other factors, perhaps resulting in an increased risk for falls, are involved. In a meta-analysis of three prospective studies in a total of 5,939 men and 11,032 women, followed for 75,433 person-years [92], alcohol consumption was non-linearly associated with an increased fracture risk. Consumption of 2 units or less (1 unit = 10 g ethanol) per day was not associated with an increased fracture rate, whereas higher alcohol intake was associated both in men and women with an increased risk of any fracture (risk ratio (RR) = 1.23; 95% CI, 1.06–1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16–1.65), or hip fracture (RR = 1.68; 95% CI, 1.19–2.36). A similar threshold of around 2 units per day for the association of alcohol intake and fracture risk was reported in earlier studies [93, 94]. At variance with the findings in some other studies, there were no significant difference between gender for either the risk ratios or threshold; above the threshold, there was a dose–effect. Also at variance with some other studies reporting a J-shaped association between alcohol consumption and fracture risk, fracture risk was not higher in subjects abstaining from alcohol use as compared with those consuming 1or 2 units per day [79, 92]. However, it should be noted that a number of both cross-sectional and prospective studies failed to detect an increased fracture risk associated with alcohol intake (see reference [1] for review).

Smoking has adverse skeletal effects and current smoking is associated with an increased fracture risk [79]. Albeit it has been reported that the adverse effects on BMD are apparent after the age of 50 and increase with age [95], smoking has been shown to also adversely affect bone health in young individuals during bone maturation [96]. In a meta-analysis of prospective studies involving 59,232 subjects (74% women) [97], current smoking was associated with increased risk of any fracture compared with non-smokers (RR = 1.25; 95% CI, 1.15–1.36) with the highest risk observed for hip fracture (RR = 1.84; 95% CI, 1.52–2.22). The risk ratio was adjusted downward when account was taken of BMD, but remained significant (RR = 1.15 and 1.60 for any fracture and hip fracture, respectively); low BMD accounted for only 23% of the increased risk for hip fracture associated with current smoking. The fracture risk was also adjusted downward when accounting for a lower BMI in smokers, but risk ratios for any fracture and hip fracture remained above unity and significant when adjusting for either BMI or both BMI and BMD. Risk ratios associated with smoking where higher in men compared with women for any fracture and osteoporotic fracture, but not for hip fracture. Risk ratio increased with age for any fracture and osteoporotic fracture, but decreased with advancing age for hip fracture. Subjects with a history of smoking had a significantly higher fracture risk than never smokers, but a lower risk than current smokers [97].

The mechanisms of the BMD-independent increased fracture risk associated with smoking are unknown, but might hypothetically involve altered bone geometry or material property not captured by DXA evaluation [96], relative physical inactivity and co-morbidity such as chronic lung disease resulting in frailty and increased risk for falls.

In most countries, in particular in mid- and southern Europe, the diet provides only a minor part of the vitamin D requirement. A major source of vitamin D₃ is synthesis in the skin under influence of UV light, as is illustrated by the marked seasonal variations in serum 25-hydroxyvitamin D levels [98]. The reported very high prevalence of vitamin D inadequacy in particular, but not exclusively, in elderly subjects [98‐100] indicates that a low dietary intake of vitamin D is not compensated by sufficient synthesis in the skin. This might in turn result from insufficient skin exposure to the sunlight and a lesser efficacy of vitamin D synthesis in de skin of elderly persons [98]. In urban areas, pollution may contribute to the limitation of effective exposure to UV from sunlight [101].

The fact that sun exposure tend to be generally low in elderly subject is illustrated by the paradoxical finding in a multi-country study in European elderly subjects of a positive association between mean serum 25-hydroxyvitamin D levels and degree of northern latitude [94]. This is most likely explained by a generally low sun exposure, also in southern European countries, and higher vitamin D availability in the diet and/or as supplements in Northern European countries. The low sun exposure in elderly persons is related to an indoor style of living and/or clothing leaving little skin exposed. In this regard, there are groups that are at higher risk of vitamin D deficiency, already at younger age, as a consequence of their habit to wear clothing that (nearly) completely covers the skin for traditional cultural and/or religious reasons [102, 103]; in these high-risk groups, high prevalence of vitamin D deficiency during pregnancy is of particular concern in view of the potential adverse skeletal consequences for mother and child.

A Single randomized controlled trial in a psychogeriatric institution in the Netherlands showed that UV irradiation of 1,000 cm² skin of the back of elderly subjects three times per week with half the minimal erythematous dose was as effective as a daily oral dose of 400 IU vitamin D₃ to raise serum levels of 25-hydroxyvitamin D and suppress secondary hyperparathyroidism [104]. Although, this proof of concept with UV irradiation approach is conceptually interesting, oral supplementation remains a more practical solution to prevent or treat vitamin D insufficiency. Moreover, present recommendations suggest higher dosing of vitamin D supplements and besides feasibility, the skin safety of the required equivalent, more extensive UV irradiation might become an issue. Along the same line, although more time spent outdoor and moderate sun exposure should be encouraged in elderly subjects in reasonably good general health, advising a marked increase of exposure to sunlight might be a somewhat confusing message, at odds with advices concerning the prevention of skin cancer. Anyhow, it is unlikely that to encourage increased exposure to sunlight could alleviate the need for oral vitamin D supplementation.

As to physical inactivity, the use of hypnotic and sedative drugs, and inappropriate housing conditions, four important risk factors for fracture related to lifestyle, these are discussed in the sections on exercise and prevention of falls.

Although there undoubtedly exist interactions between different lifestyle-related influences on bone health and fracture risk, available information on such interactions is rather limited. Nevertheless, it has been shown for several of these that they contribute at least to some extent independently to fracture risk, also independently from the effect of low BMD and high age: i.e. low BMI, excess alcohol consumption, and actual smoking [79].

Between 28% and 35% of adults aged 65 years and older and living in the community experience at least one fall each year, and the annual fall prevalence increases with ageing [105, 106]. Between 10% and 31% are recurrent fallers [107, 108]. More importantly, community-dwelling persons with dementia have the highest risk for falls with prevalence rates up to 66%, with clear differences depending on the subtype of dementia (e.g. prevalence of falls in Alzheimer’s disease 47%, vascular dementia 47%, Lewy body dementia 77%, and Parkinson’s disease dementia 90%, respectively) [109].

For those living in nursing care facilities, the annual risk of falls has been estimated to be also three times higher (i.e. up to 70%), and 15% to 40% are recurrent with rates between 1.1 and 1.4 per person per year for non-psychogeriatric residents and between 2.1 and 2.4 per person per year for psychogeriatric residents [107, 110].

But falls represent a frequent and serious problem in hospitals as well, with a variability in the incidence of falls depending on ward type and hospital population (between 2.2 and 17.1 falls per 1,000 patient days). Patients most likely to fall are older inpatients: approximately 2% to 12% of all patients experience at least one fall during their hospital stay, but this proportion may increase to 11.9% and 24.8% in geriatric wards and to even 46% in stroke rehabilitation units, respectively [111‐115].

Falls in older persons are associated with considerable mortality and morbidity. Unintentional injuries are the fifth most important cause of death in people aged 75 and over [106, 116]. Falls are the commonest cause of these unintentional injuries in this age group: 30–50% of falls result in minor trauma, 10–15% lead to serious injuries with around 5–10% resulting in fracture, and 1–2% of these being hip fractures [106]. The risk for (additional) injuries increases when fallers are unable to rise without help and when lying on the floor for a long time. Between 50% and 80% of older persons are unable to get up after at least one fall, with the higher percentages reported in the very old population (age 90 years and over). Up to 30% are lying on the floor for an hour or more, leading to serious complications such as pressure sores, dehydration, hypothermia, rhabdomyolysis, admission to hospital and long-term care, and death [117, 118].

When hospitalized, other consequences are impaired rehabilitation and functional decline, and increased need of being institutionalised, e.g. a 3-fold risk for falling without a serious injury and a 10-fold risk for a serious fall injury [119]. Although not all falls lead to injuries, psychological consequences such as fear of falling are substantial and may lead to loss of confidence, fear of dependence, social isolation, depression, and increased risk of falling [120]. In community-dwelling older persons (fallers and also nonfallers), fear of falling ranges from 20% to 85% and from 15% to 55% for associated avoidance of activity, respectively, with higher rates associated with higher age, female gender, fair and poor perceived general health, and multiple falls [121].

As in all major geriatric syndromes, multiple risk factors are involved in falls with chronic predisposing and acute precipitating factors and interactions playing a crucial role. Older persons with a precarious physiological and physical balance have the potential to fall from seemingly minor physiologic, intrinsic, and/or extrinsic risk factors; and the greater the number of risk factors the greater the risk for falls [122]. The most important intrinsic risk factors are: previous falls, decreased muscle strength (upper or lower extremity), gait and balance deficits, dizziness and orthostasis, visual impairment, depression, functional and cognitive impairment, low body mass index, urinary incontinence, chronic musculoskeletal pain, female sex, and being 80 years and older. Interactions between medications (e.g. polypharmacy), psychotropic medications, and environmental risks (e.g. loose rugs, insufficient lighting) have been identified as major extrinsic risk factors [122‐125]. Importantly, fear of falling is not only a consequence of falling as noted above, but also an important psychological risk factor for falls. Fear of falling may lead to restriction of physical activities and social participation and, as a consequence, increase the risk for physical frailty and falls [126].

All these risk factors have been identified in a variety of settings and almost always in the general older population. Until recently, no high-quality studies have examined risk factors for falling specific to dementia. In the largest prospective study to date, Allan and colleagues identified non-modifiable risk factors such as a diagnosis of Lewy body disorder, longer duration of dementia and previous history of falls or recurrent falls. More importantly, they also identified potentially modifiable risk factors such as use of cardioactive medications, autonomic symptoms, symptomatic orthostatic hypotension, depression, and limitation of physical activity [109].

Although there is substantial evidence that fall prevention strategies reduce the number of falls and risk of falling in the community setting, and preliminary evidence for the residential and acute hospital setting, less evidence is available about their effectiveness in preventing fall-related injuries (e.g. sprains, bruises, and head-injuries) and fractures (e.g. arm and hip fractures) [110, 122, 127, 128]. Despite this, clinicians should use an integrated approach for fall and fracture prevention since many of the previous mentioned risk factors for falls have been shown to increase fracture risk as well [105, 122].

For community-dwelling older adults, single as well as multifactorial fall prevention strategies have been shown to effectively reduce falls in older adults.