Amount and Source of Protein Affects Risk of Osteoporosis in Older Adults

Sufficient protein is essential for musculoskeletal health, with research suggesting that those at greatest risk of loss of bone strength, and so osteoporosis, could benefit from consuming more than the recommended daily intake for the average population. From reviewing a recent study by Durosier-Izart et al. [1] in the context of the wider literature, it has been concluded that protein intake at 1.0-1.2g/kg body weight/day, primarily sourced from dairy protein, could optimise bone health in older adults, particularly post-menopausal women.

Osteoporosis, a disease characterised by bone loss, weakening and increased fragility as a result of an imbalance between formation and resorption [2], is prevalent in 3 million people in the UK [3]. It is defined as a bone mineral density (BMD) of -2.5 SD below that of a young adult, as measured by a dual-energy X-ray absorptiometry (DEXA) scan [4]. Although bone loss occurs naturally with age, a number of risk factors may accelerate reductions in BMD and increase osteoporosis risk. These include genetic factors, disease treatment such as chemotherapy, nutritional deficiencies from digestive or metabolic disorders, and low oestrogen level. The latter causes women to lose about 50% of trabecular and 30% of cortical bone within the first 10 years post-menopause [5]. However, diet and lifestyle factors, such as smoking and lack of exercise, are also significant.

The impact of osteoporosis is greater fracture risk, primarily in the hip, wrist and vertebrae. It has been suggested that 10% loss of bone mass doubles fracture risk in the vertebrae and increases it by 2.5x in the hip [6].  Consequently, 1 in 2 women and 1 in 5 men over 50 that suffer from osteoporosis break a bone [6]. Having one fracture also doubles the risk of subsequent fractures occurring [7], with about half of sufferers experiencing a second within 10 years [8]. As well as the short term effects of limited mobility during recovery, osteoporosis has a greater impact on DALYs than most types of cancer. 1,150 people die every month from hip fractures in the UK, many require long-term nursing care, and only half walk again unaided [9]. There is also a huge economic burden on the NHS as osteoporosis accounts for more days spent in hospital amongst women over 45 years than diabetes, heart disease and breast cancer [6]. The age-related nature of progressive bone loss means that the prevalence of osteoporosis is only likely to increase with an ageing population but, unlike diseases such as dementia where treatment acts to delay onset, osteoporosis can be prevented with appropriate lifestyle advice.

It is well known that protein, comprising 50% of bone volume, is essential for maintaining bone strength by forming a structural matrix within which calcium is deposited [10]. It also optimises IGF-1 levels to stimulate bone mineralisation, enhances intestinal calcium absorption, and contributes to muscle-building to reduce sarcopenia and provide skeletal support [9]. The continuous remodelling and turnover of bone means an adequate daily protein intake is required, especially as the post-translational modification of amino acids that occurs to form cross-linked collagen means their re-utilisation in new bone formation is limited [10]. To attenuate bone loss, it is therefore proposed that protein intake within the elderly should be higher than the recommended value for the average population [11].

A recent study by Durosier-Izart et al. has investigated the association between peripheral skeletal bone strength and dietary protein intake, considering both total consumption and protein source [1]. This review will discuss the conclusions they have made and the implications this could have ondietary advice for the elderly population within the context of current research.

Method

Study population

746 women, mean age 65 years, were studied, with those suffering from an active disease that affects bone turnover and muscle performance excluded.

Dietary analysis

Dietary calcium and protein intake were estimated from a modified food-frequency questionnaire (FFQ).  Total protein, animal sourced protein (dairy and non-dairy) and vegetable protein intakes were quantitated.

Bone measurements

Lumbar spine, proximal femur and distal radius BMD, bone mineral content (BMC), and lean and fat mass were measured by DEXA. BMD and microstructure were analysed at the distal radius and distal tibia of the non-dominant limb using high resolution peripheral quantitative computed tomography (HR-pQCT) and bone strength was estimated using finite element analysis (FEA) from which the failure loads of distal radius and tibia were predicted.

Statistical analysis

Total protein intake was categorised into tertiles. Association between bone variables and total protein, animal and vegetable protein, and dairy, non-dairy animal and vegetable protein intake was analysed.   

Results

Subject characteristics

Calcium intake and protein intake met or exceeded dietary recommendations for age. Two-thirds of total protein intake was from animal origin and one-quarter was from dairy. 19.7% of subjects were osteoporotic and 57.6% osteopenic. Prevalence of osteoporotic diseases was inversely associated with protein intake. Sarcopenia prevalence was significantly lower in higher tertiles of protein intake. Protein intake was positively correlated with BMI and BMD, whole body BMC and lean mass.

Results of statistical analysis

Distal radius and tibia predicted failure load were positively associated with total and animal protein intake, and tibia failure load with dairy protein intake. There was no significant association with vegetable protein. After adjustment, a positive association was found between distal radius and tibia failure load and stiffness and dairy protein intake, which was indicated to be mediated by trabecular and cortical bone microstructure.

Discussion

The study conducted by Durosier-Izart et al. found high total protein, animal and dairy protein intake to correlate with increased predicted failure load and stiffness in the peripheral skeleton with no association with high vegetable protein intake [1]. These findings are supported by recent research where it has been found that muscle and bone mass is higher in women with a protein intake >1.2g/kg body weight/day [12], and greatest bone loss is observed in lower quartiles of protein consumption [13].

There is more discussion surrounding the impact of the source of protein on bone health. Similar to the conclusions from Durosier-Izart et al., Promislow et al. has suggested that every 15g/day increase in animal protein intake increases total body BMD by 0.010g/cm² and BMD at the hip by 0.016g/cm², at the femoral neck by 0.012g/cm² at and at the spine by 0.015g/cm² [14]. This is consistent with the results from Harper, where protein increase from meat supplements, from 0.78g/kg body weight/day to 1.55g/kg body weight/day, increased IGF-1 and consequently osteoblast activity [15]. Moreover, meat protein based diet has been shown to decrease wrist fracture risk by 80%. Nonetheless, unlike some studies, Thorpe et al. found high plant-based protein diets to still reduce the risk by 68%, suggesting there are some benefits of consuming a vegetarian diet if total protein intake is adequate [16]. Despite this, there would be some concern regarding making such advice as low-meat diets can be high in oxalic acid and phytic acid, which can inhibit calcium absorption, and there can be an association with impaired vitamin B12 status, which further negatively impacts BMD [17].

One of the most debated issues when considering increasing protein intake recommendations to enhance bone strength relates to the potential for hypercalcuria. It is said that every 10g increase in dietary protein increases urinary calcium by 16mg, partly attributed to by the increase in glomerular filtration rate [18]. However, more significantly, it has been hypothesised that catabolism of sulphur containing amino acids results in a greater metabolic acid load, causing mobilisation of citrate and carbonate from bone for neutralisation and consequently increasing urinary calcium concentration [18]. In the age group of interest this effect could be amplified as the completeness of renal buffering  reduces with age [19]. The relevance of this to the study by Durosier-Izart et al. is that animal protein is generally a greater source of sulphur containing amino acids compared to plant proteins, with fruits and vegetables often being considered as more alkaline with potential as neutralising substances [19]. Research using calcium isotopes to monitor urinary calcium have in fact shown a high protein diet to reduce the fraction of urinary calcium from bone origin with no short term effects on net bone balance [20]. This is due to an increase in intestinal calcium absorption [19] and the subsequent suppression of parathyroid hormone, reducing calcium resorption from bone into the extracellular fluid. In fact, dietary protein below 0.8g/kg body weight/day has been suggested to be an amount that could cause secondary hyperparathyroidism [15]. Moreover, the isocaloric switch from carbohydrates to meat in the elderly in the study by Dawson-Hughes et al. showed no alteration in urinary calcium excretion and lower urinary N-telopeptide, a marker of bone resorption [21]. This contrasts the early evidence that suggested a more beneficial effect of vegetable proteins over animal-sourced on preventing negative calcium balance and loss of BMD.

In the further classification of protein sources, Durosier-Izart et al. found that there was a significant positive association between dairy protein consumption and both failure load and stiffness [1]. Langsetmo et al. also found that intake of dairy protein, after adjusting for BMI, is positively associated with hip BMD among men and women aged 50+ years [22]. There is less evidence in current research to support these results as investigations into protein generally focus on total, animal or meat protein. However, as dairy products are the most important dietary source of calcium in the UK diet [23], an increase in dairy protein consumption in the age group of interest is likely to have beneficial effects on bone strength that extend beyond that obtained from protein alone. The efficiency of calcium absorption from dairy, at 22-27%, and the immediate fall in parathyroid hormone level that follows [23], promotes bone formation and inhibits resorption, as further enhanced by a high phosphorous content. It has been concluded that the positive impact of dietary protein on bone health relies upon adequate calcium intake [24], which may be linked to the need to offset any additional urinary calcium losses. The Framingham Offspring Study showed that, in men and women over 55 years of age, an intake of <800mg/day calcium combined with protein intake in the highest tertile had a 2.8x greater risk of hip fracture compared to the lowest. In contrast, calcium intake of >800mg/day and protein intake in the highest tertile reduced hip fracture risk by 85% [25]. Although soy products can contain up to 300mg calcium per 100g, their calcium content is inferior to that of dairy [23], suggesting the consumption of animal, and particularly dairy, protein to be of greater benefit when considering the combined effect of protein and calcium for bone strength and prevention of osteoporosis.  

When evaluating the evidence there were two main factors to consider. Durosier-Izart et al. measured the peripheral skeleton, whereas it seems more common to consider BMD and fracture risk at the sites most frequently associated with osteoporotic fractures, namely the hip and spine. Differences in the ratio of trabecular to cortical bone in bone structures, with there being a higher proportion of trabecular bone in vertebrae than in the radius, may affect comparability of studies, with trabecular loss post-menopause being faster than that of cortical bone, hence causing increased fragility [2]. Moreover, Durosier-Izart et al. conducted research on a homogeneous female population, limiting the generalisation of the results. Within the literature there is disparity in the sex and age range of subjects. Those examining the effects of dietary protein on men and women have more variable results due to the differing osteoporosis aetiologies, with Heaney & Layman finding dietary protein to have a role in bone health solely amongst women [10]. Some studies have seen improvements in BMD and reductions in risk of fracture in both demographics, but the majority of the research focuses on women of post-menopausal age. To provide population-wide dietary advice, further research would be required to determine if the same effects are seen within men as women. Nonetheless, an increase in dietary protein intake for all elderly individuals is likely to be beneficial in reducing risk of sarcopenia and increasing intake of calcium, magnesium, potassium, zinc and phosphorous [26], even if there are fewer benefits on bone health for men. 

Impacts

After examining the study by Durosier-Izart et al. and reviewing a selection of the literature, the overall conclusion is that an increase in total, and particularly animal protein from dairy sources, increases fracture load and stiffness in post-menopausal women [1]. This suggests that it is essential for older adults to be meeting the recommended daily protein intake of 0.8g/kg body weight/day. However, it is clear that exceeding this value, consuming 1.0-1.2g/kg body weight/day protein could optimise musculoskeletal health. This amount is deemed to be sufficient to attenuate age-related loss in BMD by favouring bone formation through maintenance of nitrogen balance, yet with limited adverse effects on calcium metabolism [11]. From the study, this advice could be further extended to recommend that a high proportion of daily protein intake comes from dairy such as milk, cheese and yoghurt, also contributing to meeting calcium requirements.

The tertiles of daily total protein intake used by Durosier-Izart et al. could be translated to <3, 3-4 and >4 servings [1], therefore the practical advice would be to aim to consume at least 4 portions of protein per day, achieved by including a source in every meal. The evidence suggests that an increase in dietary protein intake within the older population, especially for post-menopausal women who suffer rapid loss of BMD in response to hormonal changes, is likely to reduce the prevalence of osteoporosis, resulting in reduced fracture risk which can cause life-long debilitation or mortality.

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