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Animal Protein Increases Bone Loss and Fracture in Postmenopausal Women – 2001

Abstract

A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group.

Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.

Sellmeyer DE, Stone KL, Sebastian A, Cummings SR
Am. J. Clin. Nutr. Jan 2001
PMID: 11124760 | Free Full Text

More recent studies and randomized trials have discredited the conclusions of this study.

There are two published comments on this study. The full text is available for both.

Protein intake and bone health: the influence of belief systems on the conduct of nutritional science.
Heaney RP
PMID: 11124741 | Free Full Text

Dietary ratio of animal to vegetable protein and rate of bone loss and risk of fracture in postmenopausal women.
Sebastian A, Sellmeyer DE, Stone KL, Cummings SR
Am. J. Clin. Nutr. Sep 2001
PMID: 11522569 | Free Full Text

Review: Melatonin Effects on Bones and Teeth

Abstract

Melatonin effects on hard tissues: bone and tooth.

Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

Liu J, Huang F, He HW
Int J Mol Sci 2013
PMID: 23665905 | Free Full Text

From the full text:

Bone remolding processes are mediated by hormones, cytokines, growth factors and other molecules [22]. One of the hormones modulating bone formation and resorption is melatonin. It is hypothesized that melatonin, perhaps through three principle actions, modulates bone metabolism. Firstly, melatonin directly affects the actions of osteoblast and osteoclast. Numerous studies documented that melatonin increases pre-osteoblast/osteoblast/osteoblast-like cell proliferation, promotes the expression of type I collagen and bone marker proteins (e.g., alkaline phosphatase, osteopontin, bone sialoprotein and osteocalcin), and stimulates the formation of a mineralized matrix in these cells [23–27]. Besides, melatonin inhibits the differentiation of osteoclasts via decreases in the expression of RANK mRNA and increases in both the mRNA and protein levels of osteo-protegerin [28,29]. Secondly, melatonin indirectly regulates bone metabolism through the interaction with systemic hormones (e.g., PTH, calcitonin, and estrogen) or other moleculars. Ladizesky et al. [15] revealed that estradiol treatment could prolong the effect of melatonin to augment bone remodeling in ovariectomized rats; it indicates that appropriate circulating estradiol levels might be needed for melatonin effects on bone. Thirdly, osteoclasts generate high levels of superoxide anions during bone resorption that contribute to the degradative process. Melatonin is a significant free-radical scavenger and antioxidant. It can clear up the free radicals generated by osteoclast during the bone resorption process and protect bone cells from oxidative attacks [18,30,31].

And:

Some studies revealed the possible etiologic role of melatonin in osteoporosis. Nocturnal plasma melatonin levels decline with age. It has also been reported that melatonin secretion decreases sharply during menopause, which is associated with post-menopausal osteoporosis [46,47]. A correlation between decreased plasma melatonin levels and an increased incidence of bone deterioration as seen in post-menopausal women has been examined [48]. Furthermore, Ostrowska et al. [49] found that a pinealectomy in rats promotes the induction of bone metabolism biomarkers. In addition, Feskanich et al. [50] reported that twenty or more years of nightshift work significantly increased the risk of wrist and hip fractures in post-menopausal women. Nightshift work leads to disturbances of melatonin secretion as well as severe circadian rhythm disruption. These observations taken together suggest that melatonin may be involved in the pathogenesis of osteoporosis.

Protein Consumption Predicts Lower Limb Bone Mass in Elderly Women

Abstract

Protein consumption is an important predictor of lower limb bone mass in elderly women.

The effect of protein intake on bone density is uncertain, and evidence exists for beneficial effects of both low and high protein intakes. The objective was to study the relation between protein consumption and bone mass in elderly women with allowance for other lifestyle factors affecting bone metabolism. We conducted a cross-sectional and longitudinal study of a population-based sample of 1077 women aged 75 +/- 3 y. At baseline, protein consumption was measured with a food-frequency questionnaire, and bone mass and structure were measured by using quantitative ultrasound of the heel. One year later, hip bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry.
Subjects consumed a mean (+/-SD) of 80.5 +/- 27.8 g protein/d (1.19 +/- 0.44 g protein/kg body wt). Regression analysis showed a positive correlation between protein intake and qualitative ultrasound of the heel and BMD after adjustment for age, body mass index, and other nutrients. The dose-response effect was best characterized by protein consumption expressed in tertiles, such that subjects in the lowest tertile (<66 g protein/d) had significantly lower qualitative ultrasound of the heel (1.3%) and hip BMD (2.6%) than did the subjects in the higher tertiles (>87 g protein/d).
These data suggest that protein intakes for elderly women above current recommendations may be necessary to optimize bone mass.

Devine A, Dick IM, Islam AF, Dhaliwal SS…
Am. J. Clin. Nutr. Jun 2005
PMID: 15941897 | Free Full Text

Protein + Exercise Improves Bone Markers in Young Adults

Abstract

Effect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor I and markers of bone turnover in young adults.

Exercise is beneficial for bone when adequate nutrition is provided. The role of protein consumption in bone health, however, is controversial. The objective was to ascertain the effect of high protein intake on insulin-like growth factor I (IGF-I) and markers of bone turnover during 6 mo of exercise training. Fifty-one subjects aged 18-25 y (28 men, 23 women) received a protein supplement (42 g protein, 24 g carbohydrate, 2 g fat) or a carbohydrate supplement (70 g carbohydrate) twice daily. Exercise consisted of alternating resistance training and running 5 times/wk. Plasma concentrations of IGF-I, insulin-like growth factor-binding protein 3, serum bone alkaline phosphatase, and urinary N-telopeptide collagen crosslink (NTx) concentrations were measured at 0, 3, and 6 mo after 24 h without exercise and a 12-h fast.Three-day diet records indicated no difference in energy intake between the groups. Average protein intakes after supplementation began in the protein and carbohydrate groups were 2.2 +/- 0.1 and 1.1 +/- 0.1 g/kg, respectively (P < 0.001). The increase in plasma IGF-I was greater in the protein group than in the carbohydrate group (time x supplement interaction, P = 0.01). There were no significant changes over time or significant differences by supplement in plasma insulin-like growth factor-binding protein 3 (44 and 40 kDa). Serum bone alkaline phosphatase increased significantly over time (P = 0.04) and tended to be higher in the protein group than in the carbohydrate group (P = 0.06). NTx concentrations changed over time (time and time squared; P < 0.01 for both) and were greater in the protein group than in the carbohydrate group (P = 0.04). Men had higher NTx concentrations than did women (74.6 +/- 3.4 and 60.0 +/- 3.8 nmol/mmol creatinine; P = 0.005). Protein supplementation during a strength and conditioning program resulted in changes in IGF-I concentrations.

Ballard TL, Clapper JA, Specker BL, Binkley TL…
Am. J. Clin. Nutr. Jun 2005
PMID: 15941900 | Free Full Text

Review: Protein Recommended Intake – 2008

Abstract

Amount and type of protein influences bone health.

Many factors influence bone mass. Protein has been identified as being both detrimental and beneficial to bone health, depending on a variety of factors, including the level of protein in the diet, the protein source, calcium intake, weight loss, and the acid/base balance of the diet. This review aims to briefly describe these factors and their relation to bone health. Loss of bone mass (osteopenia) and loss of muscle mass (sarcopenia) that occur with age are closely related. Factors that affect muscle anabolism, including protein intake, also affect bone mass. Changes in bone mass, muscle mass, and strength track together over the life span. Bone health is a multifactorial musculoskeletal issue. Calcium and protein intake interact constructively to affect bone health. Intakes of both calcium and protein must be adequate to fully realize the benefit of each nutrient on bone. Optimal protein intake for bone health is likely higher than current recommended intakes, particularly in the elderly. Concerns about dietary protein increasing urinary calcium appear to be offset by increases in absorption. Likewise, concerns about the impact of protein on acid production appear to be minor compared with the alkalinizing effects of fruits and vegetables. Perhaps more concern should be focused on increasing fruit and vegetable intake rather than reducing protein sources. The issue for public health professionals is whether recommended protein intakes should be increased, given the prevalence of osteoporosis and sarcopenia.

Heaney RP, Layman DK
Am. J. Clin. Nutr. May 2008
PMID: 18469289 | Free Full Text

Protein Increases Calcium Absorption and Retention From a Low-Calcium Diet – 2009

Abstract

Dietary protein and calcium interact to influence calcium retention: a controlled feeding study.

The effect of meat protein on calcium retention at different calcium intakes is unresolved. The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium.In a randomized controlled feeding study with a 2 x 2 factorial crossover design, healthy postmenopausal women (n = 27) consumed either approximately 675 or approximately 1510 mg Ca/d, with both low and high protein (providing 10% and 20% energy) for 7 wk each, separated by a 3-wk washout period. After 3 wk, the entire diet was extrinsically labeled with (47)Ca, and isotope retention was monitored by whole-body scintillation counting. Clinical markers of calcium and bone metabolism were measured.
High compared with low dietary protein significantly increased calcium retention from the low-calcium (29.5% compared with 26.0% absorbed) but not the high-calcium diet (18% absorbed). For the low-calcium diet, this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion. Protein-related calciuretic effects were independent of dietary calcium. Testing at 1, 2, 3, 5, and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion. High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase, or tartrate-resistant acid phosphatase.
In healthy postmenopausal women, a moderate increase in dietary protein, from 10% to 20% of energy, slightly improved calcium absorption from a low-calcium diet, nearly compensating for a slight increase in urinary calcium excretion. Under practical dietary conditions, increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health.

Hunt JR, Johnson LK, Fariba Roughead ZK
Am. J. Clin. Nutr. May 2009
PMID: 19279077 | Free Full Text

Protein Associated with Reduced Hip Fracture in Women

Abstract

Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women.

The role of dietary protein intake in osteoporosis remains controversial. Protein is an important structural component of bone and protein supplementation improves the medical outcome of hip fracture patients, but it is unknown whether protein intake can reduce the incidence risk of hip fracture.
The relation between intake of protein and other nutrients and subsequent incidence of hip fracture was evaluated.
Nutrient intake was assessed with a food-frequency questionnaire in a cohort of Iowa women aged 55-69 y at baseline in 1986. Incident hip fractures were ascertained through follow-up questionnaires mailed to participants in 1987 and 1989 and verified by physician reports.
Forty-four cases of incident hip fractures were included in the analyses of 104338 person-years (the number of subjects studied times the number of years of follow-up) of follow-up data. The risk of hip fracture was not related to intake of calcium or vitamin D, but was negatively associated with total protein intake. Animal rather than vegetable sources of protein appeared to account for this association. In a multivariate model with inclusion of age, body size, parity, smoking, alcohol intake, estrogen use, and physical activity, the relative risks of hip fracture decreased across increasing quartiles of intake of animal protein as follows: 1.00 (reference), 0.59 (95% CI: 0.26, 1.34), 0.63 (0.28, 1.42), and 0.31 (0.10, 0.93); P for trend = 0.037.
Intake of dietary protein, especially from animal sources, may be associated with a reduced incidence of hip fractures in postmenopausal women.

Munger RG, Cerhan JR, Chiu BC
Am. J. Clin. Nutr. Jan 1999
PMID: 9925137 | Free Full Text

Protein > 95 Grams Associated With Forearm Fracture in Women

Abstract

Protein consumption and bone fractures in women.

Dietary protein increases urinary calcium losses and has been associated with higher rates of hip fracture in cross-cultural studies. However, the relation between protein and risk of osteoporotic bone fractures among individuals has not been examined in detail. In this prospective study, usual dietary intake was measured in 1980 in a cohort of 85,900 women, aged 35-59 years, who were participants in the Nurses’ Health Study. A mailed food frequency questionnaire was used and incident hip (n = 234) and distal forearm (n = 1,628) fractures were identified by self-report during the following 12 years. Information on other factors related to osteoporosis, including obesity, use of postmenopausal estrogen, smoking, and physical activity, was collected on biennial questionnaires. Dietary measures were updated in 1984 and 1986. Protein was associated with an increased risk of forearm fracture (relative risk (RR) = 1.22, 95% confidence interval (Cl) 1.04-1.43, p for trend = 0.01) for women who consumed more than 95 g per day compared with those who consumed less than 68 g per day. A similar increase in risk was observed for animal protein, but no association was found for consumption of vegetable protein. Women who consumed five or more servings of red meat per week also had a significantly increased risk of forearm fracture (RR = 1.23, 95% Cl 1.01-1.50) compared with women who ate red meat less than once per week. Recall of teenage diet did not reveal any increased risk of forearm fracture for women with higher consumption of animal protein or red meat during this earlier period of life. No association was observed between adult protein intake and the incidence of hip fractures, though power to assess this association was low.

Feskanich D, Willett WC, Stampfer MJ, Colditz GA
Am. J. Epidemiol. Mar 1996
PMID: 8610662 | Free Full Text

Review: Protein + Calcium – March 2003

Abstract

Interaction of dietary calcium and protein in bone health in humans.

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

Dawson-Hughes B
J. Nutr. Mar 2003
PMID: 12612168 | Free Full Text

Review: Vitamin D + Isoflavones may be Synergistic

Abstract

Vitamin D interactions with soy isoflavones on bone after menopause: a review.

Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.

Park CY, Weaver CM
Nutrients Nov 2012
PMID: 23201836 | Free Full Text