Bone Health

Protein and Bone Health

Historically, conflicting evidence has characterized protein as being both detrimental and beneficial to bone health, depending on the amount of protein ingested (high-protein vs low-protein diets) and the source of protein (animal vs vegetable).³⁰ Dietary protein represents a key nutrient in skeletal health as it affects bone in several ways: (1) it constitutes a large component of the organic structural matrix of bone, (2) it regulates serum concentrations of insulin-like growth factor (IGF)-1, and (3) it can affect calcium metabolism (calcium excretion and absorption).^7,30,84

Early research suggested that high-protein diets were detrimental to skeletal health, as hypercalciuria occurred in a majority of studies after individuals consumed diets high in protein.^{3,12,32,61,103} Ostensibly, the consumption of animal proteins in particular could result in a substantial increase in metabolic acid production, which would necessitate the dissolution of bone mineral to neutralize the incursion of acid. It was theorized that, over time, this process would accelerate loss of bone mineral mass and increase the risk of skeletal fracture.⁷

An increase in calcium excretion, however, does not necessarily equate to calcium loss, negative calcium balance, and reduced bone mass. Calcium absorption must also be considered. For example, Kerstetter et al⁴⁵ reported that eating a high protein diet (2.1 g of protein per 1 kg body mass) increased urinary calcium excretion, but also significantly increased intestinal calcium absorption. They hypothesized that increased absorption, and not skeletal mineral dissolution, was the main source of the elevated calcium excretion observed after ingesting high amounts of protein. Others supported that theory by arguing that the metabolic acid load, induced by consuming large amounts of protein, could be managed by the highly efficient mechanisms of hydrogen ion removal via the lung and kidney, as well as renal bicarbonate retention, without having to resort to the skeletal tissue, barring kidney or lung failure.⁷

Similarly, many studies have reported that high-protein diets were linked to the increased production of IGF-1, a key osteotrophic growth factor,^30,84 increased bone mineral content, decreased risk of fracture, and increased fracture repair after injury.^13,27,67 Higher-protein diets are also recommended for adolescent and child athletes undergoing strenuous training, as protein requirements are larger because of the process of bone modeling and growth, as well as the intensity of physical activity. Inadequate protein consumption in this group can attenuate the skeleton’s anabolic response to mechanical loading and may be detrimental to bone structure and strength.¹⁰⁵

Diets lower in protein (0.7-0.8 g/kg) can be associated with elevated serum levels of parathyroid hormone (PTH), secondary to reduced intestinal calcium absorption, even with adequate calcium supplementation.^44,45 A threshold effect was apparent, as protein levels below 0.9 g/kg were associated with disrupted mineral homeostasis.⁴⁷ General agreement exists that diets moderate in protein (1.0-1.5 g/kg) are associated with normal calcium metabolism, which presumably does not alter skeletal homeostasis.⁴⁶ Collectively, these data suggest that adequate protein is essential for developing and maintaining healthy skeletal tissue. Moreover, maintenance of adequate bone strength for high-performance activities is tightly linked to maintenance of adequate muscle mass and function, which is dependent on adequate intake of high-quality protein.^30,98

In addition to quantity of protein, dietary protein source has also been a topic of controversy relative to bone health. The notable claim that animal proteins generate more acid and, therefore, are more calciuritic than vegetable proteins has recently been questioned. This hypothesis proposes that the sulfur content (from sulfur-containing amino acids) of animal proteins is greater than that of vegetable proteins and hence, the production of sulfuric acid from the metabolism of animal proteins would also be greater.^7,62 However, Bonjour⁷ argues that this line of reasoning falters when considering a basic chemical analysis of the sulfur content of different proteins. The potential acid formation as sulfate was calculated, based on amino acid composition, for animal and vegetable proteins⁶²: 82, 69, and 68 mEq/100 g protein for oatmeal, whole wheat, and white rice, respectively; and 73, 59, and 55 mEq/100 g protein in pork, beef, and milk, respectively. Bonjour’s research, numerous clinical trials,^46,85 and a controlled feeding study that reported no change in urinary calcium excretion when soy protein was replaced with meat protein in postmenopausal women⁸¹ suggest that intestinal calcium absorption as determined by overall volume of protein intake is a much stronger determinant of urine calcium excretion than protein source, whether it be from plant or animal origins.⁷

Dietary Fat and Bone Health

In addition to protein, dietary fat in relation to bone health has also been investigated (mainly in terms of fatty acid composition). Many early nutritional studies were conducted to better understand the relation between saturated fat consumption and bone health. The relation between fat consumption and calcium absorption in a growing animal model was examined to determine whether fat favored or hindered calcium absorption in the gut.^21,40,42,88 French²¹ used young male albino rats on diets with varying percentages of saturated fat (5%, 14%, 28%, and 45%) to substantiate claims that poor calcium absorption resulted from the formation of indigestible calcium-saturated fatty acid complexes within the intestine. Absorption of calcium decreased moderately and consistently with increasing fat content (5%-28%), with a considerable decline in intestinal calcium absorption in the 45% fat diet. Whether the decrease in calcium absorption led to decrements in skeletal strength was not reported.

Similar results have been reported in human populations. Corwin et al¹⁴ reported a negative association between saturated fat intake and hip bone mineral density (BMD) in both men and women using NHANES III (Third National Health and Nutrition Examination Survey) data (n = 14 850). After adjusting for age, sex, weight, height, race, total energy and calcium intake, smoking, and weightbearing exercise, the greatest effects were seen in men under the age of 50 years in the femoral neck, where individuals in the highest quintile of saturated fat consumption had a mean femoral neck BMD that was 4.3% less than the individuals in the lowest quintile of consumption.

Simple Carbohydrates and Bone Health

With diets high in refined sugar, the monosaccharide glucose and the disaccharide sucrose are the simple carbohydrate models that have been extensively studied. Results of many earlier studies examining glucose consumption and calcium excretion agreed that upon ingestion of glucose, calciuria was exaggerated.^18,53 Lemann et al⁵³ used healthy male subjects to investigate how glucose consumption affected urinary calcium excretion, and whether mineral loss was due to an increased glomerular filtration rate (GFR) or reduced net renal tubular reabsorption in the kidney. Despite a decrease in GFR upon standing from a recumbent position, urine excretion of calcium increased significantly for individuals administered an oral glucose solution. Glucose ingestion may (directly or indirectly) have an alteration of renal cell metabolism in the region of the distal tubule of the kidney, affecting net calcium reabsorption.

Other theories about how glucose could affect calcium metabolism have also been suggested. Ericsson et al²⁰ reported exaggerated urinary calcium loss in young adult humans after consumption of a glucose solution. Lactic acids, formed by osteoclast metabolism of glucose molecules, may have potentially dissolved calcium and magnesium salts from adjacent bone surfaces, resulting in greater than normal calcium excretion in the urine. Alternatively, glucose in high concentrations could have a direct inhibitory effect on osteoblast proliferation and differentiation in vitro.⁸⁹

In addition to implicating glucose/sucrose directly for altering renal cell metabolism, others suggest that inhibition of calcium reabsorption is mediated by the insulin response to diet. In human and animal models, an insulin spike preceded peak calcium clearance and demonstrated strong, positive correlations between serum insulin levels and urinary calcium excretion. More specifically, hypercalciuria induced by glucose could be 80% inhibited with the administration of mannoheptulose, a drug that suppresses insulin secretion.^35,99 Potentially, the effect of insulin may be direct, affecting renal calcium transport by means of a calcium ATPase (an enzyme that catalyzes adenosine triphosphate [ATP] into adenosine diphosphate [ADP]) pump located on the basal-lateral membrane of the renal cell wall.⁴⁹ Because insulin can inhibit calcium ATPase in adipocytes,⁷⁶ a similar effect may be experienced in renal cells leading to a calciuritic response to hyperinsulinemia.

Refined carbohydrates affect bone growth and mechanical strength. Tjaderhane and Larmas⁹¹ studied growing male and female Wistar rats to test skeletal mechanical integrity in groups fed a control or high-sucrose diet. The breaking strengths of the tibiae and femurs were significantly lower in the sucrose-fed group in both sexes when compared to controls, and skeletal degradation was more prominent in females, independent of body weight.

Their data were augmented by studies^54,83,104 quantifying the effect of diets high in both saturated fat and sucrose (HFS) on bone mechanics and mineralization. Li et al⁵⁴ found that cortical bone exposed to an HFS diet had significantly lower maximal load and failure energies as well as decreased tensile stress at the proportional limit when compared to control samples after 10 weeks. Similar decrements in mechanical strength and bone quality were documented in the axial skeleton (vertebrae), in growing and skeletally mature animal models, and over short- and long-term studies.^54,83,104 Cancellous bone, such as vertebrae, was more adversely affected than cortical bone, such as tibia, likely because of its proximity to vasculature and its accelerated rate of bone turnover.⁸³

Consumption of carbonated beverages, such as soft drinks, is associated with significant decreases in bone mineral density in both males and females.^100-102 Potential negative effects of carbonated soft drinks on bone have been linked primarily with the caffeine²³ and sugar content^75,92 found in these drinks. Changes in bones due to the consumption of soft drinks may be due to the concomitant decreased consumption of milk and other fluids.³¹ For example, a study conducted by Ogur et al⁷⁵ on growing male and female Sprague-Dawley rats found that water consumption was decreased 6-fold in rats fed cola beverages, supporting claims that reduced consumption of nutrient-dense fluids may contribute to the negative effects observed in children and adolescents habitually consuming soft drinks.^100,101 Moreover, these authors found that consuming cola beverages was associated with substantial increases in triglycerides, very low-density lipoproteins, and body mass, in concert with decreases in triiodothyronine (T₃), thyroxine (T₄), and blood iron levels.⁷⁵ Femoral BMD was lower in the cola-fed groups versus controls. These data suggest a decrease in lean tissue, concomitant with an increase in fat mass in the cola-fed subjects. Moreover, cola consumption can enhance the loss of 2 micronutrients (calcium and iron) crucial to health and performance that are already likely to be low in the diets of athletes, especially young ones.⁶³

More recently, a study was conducted to investigate the effects of feeding different sugar-sweetened beverages on bone mass and strength in growing rats.⁹² Rats were randomly assigned to consume either deionized, distilled water (ddH₂O; control) or a ddH₂O containing 13% w/v (weight/volume) glucose, sucrose, fructose, or high-fructose corn syrup (HFCS)-55 for 8 weeks. Tsanzi et al⁹² reported the 13% glucose solution had the most profound negative effects on the rats versus the fructose-sweetened beverage, which did not differ significantly from controls. Glucose consumption led to polydipsia, which led to a significant reduction in food and associated mineral ingestion, despite increased caloric intake. As a result, calcium and phosphorus intake was decreased, and calcium excretion was increased. Bone mineral density, bone mineral content (BMC), and total phosphorus content of whole femurs and tibiae were significantly lower in rats fed a 13% glucose solution versus fructose solution. Moreover, rats consuming the fructose solution had higher calcium intake, lower calcium excretion, and higher calcium retention versus the glucose-fed group,⁹² supporting previous findings reported in a human study by Milne and Nielson⁶⁵ that found that bone alkaline phosphatase, a marker of bone formation, was increased with high fructose intake. Thus glucose, rather than fructose, exerts more deleterious effects on mineral balance and bone.

Of specific interest to athletes, these results have implications about the consumption of sports drinks. According to the aforementioned study, the authors suggested that the glucose/fructose ratio found in HFCS is important. For example, soft drinks use HFCS-55, a compilation of 55% fructose, 42% glucose, and 3% complex saccharides.³³ This sweetener (HFCS-55) did not negatively affect the rat skeleton at any of the tested sites in the study conducted by Tsanzi et al.⁹² However, sports drinks (eg, Gatorade or Powerade), often consumed by athletes to replenish energy and electrolytes, commonly use HFCS-42, which contains 42% fructose and 58% glucose.³³ As the glucose/fructose ratio is greater in sports drinks, it has been suggested that these beverages may potentially exert larger negative effects on the skeleton than drinks comprised of a higher proportion of fructose. Indeed, sports drink consumption has been linked with significant erosion of tooth tissue in vitro.⁷⁸ Hence it may be worthwhile to promote the consumption of fluids without glucose, such as bottled or tap water, milk or soy-based solutions, or fluids containing greater proportions of fructose to glucose, such as orange juice, or sports drinks fortified with calcium to prevent losses in BMD in this population.

Fats and Carbohydrates Beneficial to Bone Health

Some evidence notwithstanding, it is important to recall that not all fats and carbohydrates are detrimental to skeletal health. On the contrary, optimal quantities of polyunsaturated fatty acids (PUFAs), such as omega-3 fatty acid chains, may inhibit the activities of osteoclasts and enhance the activities of osteoblasts in animals, thus appearing to impede bone resorption and promote bone formation.^87,93 Moreover, in a recent controlled feeding study using human participants, diets high in plant-derived PUFAs were associated with decreased markers of bone resorption after 6 weeks.²⁴ Self-reported omega-3 intake correlated with femoral neck BMD in 247 older men and women. Individuals reporting higher consumption of omega-3 fatty acids had significantly higher hip BMD than subjects reporting lower intake (<1.27 g/d).⁸²

Complex carbohydrates, such as in fruits and vegetables, can augment skeletal growth by increasing calcium absorption and neutralizing metabolic acid loads with their substantial potassium content.⁷¹ Many fruits and vegetables contain nondigestible carbohydrates, such as inulin-type fructans, which cannot be digested by mammalian enzymes.¹⁷ As these molecules cannot be broken down in the small intestine, they travel to the colon where they ferment to produce numerous organic acids, essentially lowering the luminal pH of the large intestine. The reduction in pH alters calcium speciation, which increases calcium solubility in the lumen, largely amplifying calcium bioavailability and enhancing passive transport into the body.¹⁶ Inulins have also been reported to indirectly enhance epithelial cell growth, thus increasing absorptive area within the large and small intestine.⁷⁹

Large increases in calcium absorption have been noted with the addition of dietary inulins in young adults (58% increase in calcium absorption in response to 40 g/d of inulin after 24 d)¹⁵ as well as in postmenopausal women (42% increase after consuming 8 g/d of inulins for 3 months).⁴⁸ It is unclear whether the increases in calcium absorption will impact bone metabolism, but 1 clinical trial investigating this question in adolescent males found that after 1 year of inulin supplementation (8 g/d), total body BMC and BMD were higher in the inulin-supplemented group versus controls.¹