Jane E. Kerstetter

Nutrition in bone health revisited: a story beyond calcium.

Osteoporosis is a complex, multi-factorial condition characterized by reduced bone mass and impaired micro-architectural structure, leading to an increased susceptibility to fractures. Although most of the bone strength (including bone mass and quality) is genetically determined, many other factors (nutritional, environmental and life-style) also influence bone. Nutrition is important modifiable factor in the development and maintenance of bone mass and the prevention and treatment of osteoporosis. Approximately 80–90% of bone mineral content is comprised of calcium and phosphorus. Other dietary components, such as protein, magnesium, zinc, copper, iron, fluoride, vitamins D, A, C, and K are required for normal bone metabolism, while other ingested compounds not usually categorized as nutrients (e.g. caffeine, alcohol, phytoestrogens) may also impact bone health. Unraveling the interaction between different factors; nutritional, environmental, life style, and heredity help us to understand the complexity of the development of osteoporosis and subsequent fractures. This paper reviews the role of dietary components on bone health throughout different stages of life. Each nutrient is discussed separately, however the fact that many nutrients are co-dependent and simultaneously interact with genetic and environmental factors should not be neglected. The complexity of the interactions is probably the reason why there are controversial or inconsistent findings regarding the contribution of a single or a group of nutrients in bone health.

Dietary protein, calcium metabolism, and skeletal homeostasis revisited

High dietary protein intakes are known to increase urinary calcium excretion and, if maintained, will result in sustained hypercalciuria. To date, the majority of calcium balance studies in humans have not detected an effect of dietary protein on intestinal calcium absorption or serum parathyroid hormone. Therefore, it is commonly concluded that the source of the excess urinary calcium is increased bone resorption. Recent studies from our laboratory indicate that alterations in dietary protein can, in fact, profoundly affect intestinal calcium absorption. In short-term dietary trials in healthy adults, we fixed calcium intake at 20 mmol/d while dietary protein was increased from 0.7 to 2.1 g/kg. Increasing dietary protein induced hypercalciuria in 20 women [from 3.4 +/- 0.3 ( +/- SE) during the low-protein to 5.4 +/- 0.4 mmol/d during the high-protein diet]. The increased dietary protein was accompanied by a significant increase in intestinal calcium absorption from 18.4 +/- 1.3% to 26.3 +/- 1.5% (as determined by dual stable isotopic methodology). Dietary protein intakes at and below 0.8 g/kg were associated with a probable reduction in intestinal calcium absorption sufficient to cause secondary hyperparathyroidism. The long-term consequences of these low-protein diet-induced changes in mineral metabolism are not known, but the diet could be detrimental to skeletal health. Of concern are several recent epidemiologic studies that demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low-protein diets. Studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation, or both.

Increasing dietary protein requirements in elderly people for optimal muscle and bone health.

Osteoporosis and sarcopenia are degenerative diseases frequently associated with aging. The loss of bone and muscle results in significant morbidity, so preventing or attenuating osteoporosis and sarcopenia is an important public health goal. Dietary protein is crucial for development of bone and muscle, and recent evidence suggests that increasing dietary protein above the current Recommended Dietary Allowance (RDA) may help maintain bone and muscle mass in older individuals. Several epidemiological and clinical studies point to a salutary effect of protein intakes above the current RDA (0.8 g/kg per day) for adults aged 19 and older. There is evidence that the anabolic response of muscle to dietary protein is attenuated in elderly people, and as a result, the amount of protein needed to achieve anabolism is greater. Dietary protein also increases circulating insulin‐like growth factor, which has anabolic effects on muscle and bone. Furthermore, increasing dietary protein increases calcium absorption, which could be anabolic for bone. Available evidence supports a beneficial effect of short‐term protein intakes up to 1.6 to 1.8 g/kg per day, although long‐term studies are needed to show safety and efficacy. Future studies should employ functional measures indicative of protein adequacy, as well as measures of muscle protein synthesis and maintenance of muscle and bone tissue, to determine the optimal level of dietary protein. Given the available data, increasing the RDA for older individuals to 1.0 to 1.2 g/kg per day would maintain normal calcium metabolism and nitrogen balance without affecting renal function and may represent a compromise while longer‐term protein supplement trials are pending. J Am Geriatr Soc 57:1073–1079, 2009.

Low Dietary Protein and Low Bone Density

Relatively little is known about the effects of low dietary protein intake on bone health. We have reported that in healthy young women, 4 days of a low-protein diet decreased urinary calcium excretion and was accompanied by secondary hyperparathyroidism (2 0 HPT) with twothreefold increases in serum PTH, 1,25(OH) 2 vitamin D, and nephrogenous cyclic adenosine monophosphate excretion (a bio-index of PTH action). The low-protein diet contained 45 g of protein (0.7 g/kg), 800 mg calcium, and was otherwise well balanced. The 2 0 HPT and reduced urinary calcium persisted for at least 2 weeks [1]. The etiology of the 20 HPT is due, in part, to a significant reduction in intestinal calcium absorption as measured by dual stable calcium isotopes [2]. We have observed that young women absorbed an average of 19% of dietary calcium after consuming the reduced protein diet for 4 days [2]. The longterm implications of these findings are uncertain, however, there is a clear potential to affect bone health. Data from the recently completed third National Health and Nutrition Examination Survey (NHANES III) [3] included information on protein intake and bone mineral density (BMD), and we therefore examined the relationship between these two parameters. Figure 1 shows mean total hip BMD, determined by dual energy X-ray absorptiometry (DXA), in 1822 non-Hispanic white women ages 50 years and older from NHANES III. Mean protein intakes (g/day ± SD) in each quartile were 31 ± 8, 50 ± 4, 65 ± 5, and 96 ± 22, respectively. After adjusting for age and body weight, there was a significant overall effect of protein intake ( P 4 0.037). A dietary protein intake in the lowest quartile (0–43 g/day) was associated with a significantly reduced BMD in the femur as compared with the quartile with the highest intake (>75 g/day); P 4 0.003. Women with intakes in the second quartile (44–58 g/day) also had significantly reduced BMD values compared with the highest quartile ( P 4 0.028). The same pattern occurred when the sample was restricted to women with calcium intakes

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial

800 mg/day, which suggests that the relationship observed between dietary protein and BMD is probably not due to the effects of a concurrently low calcium intake. The mechanisms that underlie the apparent association of low protein intakes with low BMD are unknown. Our experimental data suggest one possibility which is that persistent 2 0 HPT and diminished calcium absorption at low levels of dietary protein intake cause a reduction in BMD due to the combined effects of calcium insufficiency and increased skeletal effects of PTH.

Determination of calcium salt solubility with changes in pH and PCO2, simulating varying gastrointestinal environments

BACKGROUND Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. DESIGN We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.

Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial.

The amount of calcium available for absorption is dependent, in part, on its sustained solubility in the gastrointestinal (GI) tract. Many calcium salts, which are the calcium sources in supplements and food, have pH‐dependent solubility and may have limited availability in the small intestine, the major site of absorption. The equilibrium solubility of four calcium salts (calcium oxalate hydrate, calcium citrate tetrahydrate, calcium phosphate, calcium glycerophosphate) were determined at controlled pH values (7.5, 6.0, 4.5 and ≤ 3.0) and in distilled water. The solubility of calcium carbonate was also measured at pH 7.5, 6.0 and 4.5 with two CO2 environments (0.3 and 152 mmHg) above the solution. The precipitation profile of CaCO3 was calculated using in‐vivo data for bicarbonate and pH from literature and equilibrium calculations. As pH increased, the solubility of each calcium salt increased. However, in distilled water each salt produced a different pH, affecting its solubility value. Although calcium citrate does have a higher solubility than CaCO3 in water, there is little difference when the pH is controlled at pH 7.5. The partial pressure of CO2 also played a role in calcium carbonate solubility, depressing the solubility at pH 7.5. The calculations of soluble calcium resulted in profiles of available calcium, which agreed with previously published in‐vivo data on absorbed calcium. The experimental data illustrate the impact of pH and CO2 on the solubility of many calcium salts in the presence of bicarbonate secretions in the intestine. Calculated profiles using in‐vivo calcium and bicarbonate concentrations demonstrate that large calcium doses may not further increase intestinal calcium absorption once the calcium carbonate solubility product has been reached.

Calcium Intake in the United States from Dietary and Supplemental Sources across Adult Age Groups: New Estimates from the National Health and Nutrition Examination Survey 2003-2006

Proton pump inhibitors (PPIs) are the most potent gastric acid suppressing drugs available, and their use is widespread. An emerging concern about chronic PPI therapy is whether these drugs impair intestinal calcium absorption, resulting in a negative calcium balance and thereby potentially causing bone loss. The objective of this study was to evaluate the acute effect of the PPI esomeprazole or placebo on intestinal calcium absorption in healthy adults. Twelve young adults participated in a placebo‐controlled, double‐blind, crossover study. There were two 3‐week interventions that included a 14‐day adjustment period (designed to stabilize calcium homeostasis) followed by 6 days of a diet containing 800 mg of calcium and 2.1 g/kg of protein (intervention). During the last 3 days of the adjustment period and throughout the intervention period, subjects consumed esomeprazole or placebo. Half the subjects underwent 24‐hour continuous gastric acid pH monitoring. Intestinal calcium absorption was measured using dual‐stable calcium isotopes at the end of each intervention. Treatment with esomprazole significantly increased gastric pH (mean pH on PPI 5.38 ± 0.13, mean pH on placebo 2.70 ± 0.44, p = .005). Neither calcium absorption (PPI 34.2% ± 2.4%, placebo 31.5% ± 2.1%, p = .24) nor urinary calcium (PPI 321 ± 38 mg/34 hours, placebo 355 ± 37 mg/34 hours, p = .07) differed between the PPI and placebo groups. It is concluded that short‐term gastric acid suppression by PPIs does not attenuate intestinal calcium absorption in healthy young adults.

Adequate dietary protein is associated with better physical performance among post-menopausal women 60-90 years

BACKGROUND Adequate lifelong calcium intake is essential in optimizing bone health. Recent National Health and Nutrition Examination Survey data were used to quantify variation in calcium intake across adult age groups and to relate age-associated changes in calcium intake with energy intake. Additional goals were to assess differences in dietary calcium intake between supplemental calcium users and nonusers and to evaluate associations between age and calcium density in the diet. DESIGN This cross-sectional analysis determined calcium and energy intake for National Health and Nutrition Examination Survey respondents during 2003-2006. Diet was assessed with 24-hour recall and supplement use via questionnaire. Trends in median intakes for dietary calcium, total calcium, and energy across age categories were assessed using survey analysis methods. Nutrient density was represented using calcium to energy intake ratios. RESULTS The analyses included data from 9,475 adults. When compared to the 19- to 30-year age group, median dietary calcium intake was lower in the ≥81-year age group by 23% in men (P<0.001) and by 14% in women (P=0.003). These reductions coincided with 35% and 28% decreases, respectively, in median energy intake (P<0.001 for each sex). In contrast, the frequency of calcium supplement use increased (P<0.001) with age in both men and women. Yet, among female supplement users, the decline in median dietary calcium intake was greater than in nonusers (P=0.02). Calcium density in the diet significantly increased relative to age in men and women (P<0.001 for each sex); however, dietary and total calcium to energy ratios were insufficient to meet target ratios inferred by adequate intake standards after age 50 years. CONCLUSIONS Although supplemental calcium use and calcium density were highest in older age groups, they were not sufficient in meeting recommended levels. New approaches to increasing the frequency and level of calcium supplement use to enhance calcium density in diets may be necessary to reduce osteoporosis risk among older Americans.

Protein Intake and Calcium Homeostasis

Objectives: ObjectivesSarcopenia, the involuntary loss of skeletal muscle with age, affects up to onequarter of older adults. Evidence indicates a positive association between dietary protein intake and lean muscle mass and strength among older persons, but information on dietary proteins effect on physical performance in older adults has received less attention.DesignCross-sectional observational analysis of the relationship of dietary protein on body composition and physical performance.SettingClinical research center.Participants387 healthy women aged 60–90 years (mean 72.7 ± 7.0 y).MeasurementsMeasures included body composition (fat-free mass, appendicular skeletal mass and fat mass) via dual x-ray absorptiometry (DXA), physical performance (Physical Performance Test [PPT] and Short Physical Performance Battery [SPPB]), handgrip strength, Physical Activity Scale in the Elderly (PASE), quality of life measure (SF-8), falls, fractures, nutrient and macromolecule intake (four-day food record). Independent samples t-tests determined mean differences between the above or below RDA protein groups.Statistical AnalysisAnalysis of covariance was used to control for body mass index (BMI) between groups when assessing physical performance, physical activity and health-related quality of life.ResultsThe subjects consumed an average of 72.2 g protein/day representing 1.1 g protein/kg body weight/day. Subjects were categorized as below the recommended daily allowance (RDA) for protein (defined as less than 0.8 g protein/kg) or at or above the RDA (equal to or higher than 0.8 g protein/kg). Ninety-seven subjects (25%) were in the low protein group, and 290 (75%) were in the higher protein group. Women in the higher protein group had lower body mass, including fat and lean mass, and fat-to-lean ratio than those in the lower-protein group (p <0.001). Composite scores of upper and lower extremity strength were impaired in the group with low protein intake; SPPB score was 9.9±1.9 compared to 10.6±1.6 in those with higher protein intake and PPT was 19.8± 2.9 compared to 20.9±2.1 in the low and higher protein groups, respectively. The results were attenuated by correction for BMI, but remained significant. The physical component of the SF-8 was also lower in the low protein group but did not remain significant when controlling for BMI. No significant differences were found in hand grip strength or reported physical activity.ConclusionHealthy, older postmenopausal women consumed, on average, 1.1 g/kg/d protein, although 25% consumed less than the RDA. Those in the low protein group had higher body fat and fat-to-lean ratio than those who consumed the higher protein diet. Upper and lower extremity function was impaired in those who consumed a low protein diet compared to those with a higher protein intake. Protein intake should be considered when evaluating the multi-factorial loss of physical function in older women.