Tag Archives: human

Melatonin May Protect Against Bone Loss in Postmenopausal Women

Abstract

Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women.

Few experimental and clinical studies show that melatonin (MEL) can play a significant part to modulate circadian bone metabolism. On this basis it was suggested that MEL secretion which altered during 24-h in obese women could be of importance to regulate bony mass defect after menopause.
The aim of the study was to prove if there were any connection between changes in 24-h profile of serum MEL levels and circadian metabolism of type I collagen in postmenopausal women with visceral obesity.
The relationship of 24-h profile of salivary MEL and circadian metabolism of type I collagen (as assessed by measuring saliva concentrations of carboxyterminal propeptide of type I procollagen–PICP and cross-linked carboxyterminal telopeptide of type I collagen–ICTP) was investigated in 26 women with visceral obesity (33.5 < BMI < 42.1 kg/m(2)) and 18 healthy volunteers with correct body mass (21 < BMI < 24.5 kg/m(2); 0.73 < WHR < 0.76). The specimens were collected at subjects’ home at 3 h intervals during a 24 h span. The age range of all subjects was 52-60 years.
In all the obese women studied a tendency to suppress circadian levels of tested biochemical markers of bone metabolism was observed (especially regarding ICTP); those alterations were accompanied by substantial increment in MEL concentrations during the day. Significant and negative correlation was found between values of acrophase MEL and PICP rhythms and both amplitude and acrophase of MEL and ICTP rhythms.
Our results confirm hypothesis that alterations in MEL concentrations might have a protective effect against postmenopausal loss of bone mass.

Ostrowska Z, Kos-Kudla B, Marek B, Swietochowska E…
Neuro Endocrinol. Lett. Apr 2001
PMID: 11335888

Melatonin Increases Bone Density in Blind Mice

Abstract

Effects on bone by the light/dark cycle and chronic treatment with melatonin and/or hormone replacement therapy in intact female mice.

In this study, the effects of the light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-) fluctuate in a diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6, Bglap, and Per2 mRNA levels coincide with melatonin levels. The effect of chronic HRT (0.5 mg 17β-estradiol + 50 mg progesterone in 1800 kcal of diet) alone and in combination with melatonin (15 mg/L drinking water) on bone quality and density was also assessed by histomorphometry and microcomputed tomography, respectively. Bone density was significantly increased (P < 0.05) after 1 yr of treatment with the individual therapies, HRT (22% increase) and nocturnal melatonin (20% increase) compared to control. Hormone replacement therapy alone also increased surface bone, decreased trabecular space, and decreased the number of osteoclasts without affecting osteoblast numbers compared to the control group (P < 0.05). Chronic HRT + melatonin therapy did not significantly increase bone density, even though this combination significantly increased Bglap mRNA levels. These data suggest that the endogenous melatonin rhythm modulates markers important to bone physiology. Hormone replacement therapy with or without nocturnal melatonin in cycling mice produces unique effects on bone markers and bone density. The effects of these therapies alone and combined may improve bone health in women in perimenopause and with low nocturnal melatonin levels from too little sleep, too much light, or age.

Witt-Enderby PA, Slater JP, Johnson NA, Bondi CD…
J. Pineal Res. Nov 2012
PMID: 22639972

Melatonin Improves Formation:Resorption Ratio in Women

Abstract

Melatonin osteoporosis prevention study (MOPS): a randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women.

The purpose of this double-blind study was to assess the effects of nightly melatonin supplementation on bone health and quality of life in perimenopausal women. A total of 18 women (ages 45-54) were randomized to receive melatonin (3mg, p.o., n=13) or placebo (n=5) nightly for 6 months. Bone density was measured by calcaneal ultrasound. Bone turnover marker (osteocalcin, OC for bone formation and NTX for bone resorption) levels were measured bimonthly in serum. Participants completed Menopause-Specific Quality of Life-Intervention (MENQOL) and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after treatment. Subjects also kept daily diaries recording menstrual cycling, well-being, and sleep patterns. The results from this study showed no significant change (6-month-baseline) in bone density, NTX, or OC between groups; however, the ratio of NTX:OC trended downward over time toward a ratio of 1:1 in the melatonin group. Melatonin had no effect on vasomotor, psychosocial, or sexual MENQOL domain scores; however, it did improve physical domain scores compared to placebo (mean change melatonin: -0.6 versus placebo: 0.1, P<0.05). Menstrual cycling was reduced in women taking melatonin (mean cycles melatonin: 4.3 versus placebo: 6.5, P<0.05), and days between cycles were longer (mean days melatonin: 51.2 versus placebo: 24.1, P<0.05). No differences in duration of menses occurred between groups. The overall PSQI score and average number of hours slept were similar between groups. These findings show that melatonin supplementation was well tolerated, improved physical symptoms associated with perimenopause, and may restore imbalances in bone remodeling to prevent bone loss. Further investigation is warranted.

Kotlarczyk MP, Lassila HC, O’Neil CK, D’Amico F…
J. Pineal Res. May 2012
PMID: 22220591

Protein Lowers Fracture in 50-59 Year Olds, not 70-89 Year Olds

Abstract

Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah.

The role of protein intake in osteoporosis is unclear. In a case-control study in Utah (n = 2501), increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50-69 years of age but not in those 70-89 years of age. Protein intake may be important for optimal bone health.
Protein is an important component of bone, but the role of dietary protein intake in osteoporosis and fracture risk remains controversial.
The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah. Patients, 50-89 years of age, with hip fracture (cases) were ascertained through surveillance of 18 Utah hospitals during 1997-2001. Age- and gender-matched controls were randomly selected. Participants were interviewed in their place of residence, and diet was assessed using a picture-sort food frequency questionnaire previously reported to give a useful measure of usual dietary intake in the elderly Utah population. The association between protein intake and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases (831 women, 336 men) and 1334 controls (885 women, 449 men).
In logistic regression analyses that controlled for gender, body mass index, smoking status, alcohol use, calcium, vitamin D, potassium, physical activity, and estrogen use in women, the odds ratios (OR) of hip fracture decreased across increasing quartiles of total protein intake for participants 50-69 years of age (OR: 1.0 [reference]; 0.51 [95% CI: 0.30-0.87]; 0.53 [0.31-0.89]; 0.35 [0.21-0.59]; p < 0.001). No similar associations were observed among participants 70-89 years of age. Results from analyses stratified by low and high calcium and potassium intake did not differ appreciably from the results presented above.
Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50-69 years of age but not in men and women 70-89 years of age. The association between dietary protein intake and risk of hip fracture may be modified by age. Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50-69 years of age.

Wengreen HJ, Munger RG, West NA, Cutler DR…
J. Bone Miner. Res. Apr 2004
PMID: 15005839

Protein Supplement in Hip Rehabilitation Not Significant

Abstract

Provision of high-protein supplement for patients recovering from hip fracture.

We compared clinical outcomes with a standard (Ensure) or a high-protein (Boost HP) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital. This randomized, double-blind, parallel-group study compared the clinical effectiveness of a standard (Ensure) with a high-protein (Boost HP) liquid nutritional supplement among patients (n = 46) 60 y or older who recently underwent surgical repair of a hip fracture. Patients were encouraged to drink at least two 8-oz cans (17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge, length of rehabilitation stay, laboratory measures (i.e., serum albumin, prealbumin, and C-reactive protein), physical activity energy expenditure by 7-d triaxial accelerometry, and dietary intake by three random, telephonic, 24-h dietary recalls.
There were no significant group differences with respect to age, sex, acute hospital days, hip fracture assessment parameters, or surgical treatment. Consumption of supplement (260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP) was comparable. There were no differences in complication or adverse event rates during the study. The Boost HP group consumed more protein than the Ensure group (63 versus 50 g, P < 0.048) and had a greater improvement in serum albumin over the 28-d supplementation period (+0.7 versus +0.2 g/dL, P < 0.019). The Boost HP group also consumed more fiber (12 versus 8 g), calcium (821 versus 639 mg), vitamin K (66 versus 45 microg), and phosphorus (1035 versus 833 mg) than did the Ensure group. Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group, although this trend did not reach statistical significance (23 versus 28 d, P = 0.27). Outcome differences were not detected in the Functional Independence Measure.
Supplementation was well tolerated in this population and contributed significantly to total dietary intake. Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status.

Neumann M, Friedmann J, Roy MA, Jensen GL
Nutrition May 2004
PMID: 15105027

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 RDA May be Too Low

Abstract

Protein intake and bone health.

Adequate nutrition plays an important role in the development and maintenance of bone structures resistant to usual mechanical stresses. In addition to calcium in the presence of an adequate supply of vitamin D, dietary proteins represent key nutrients for bone health and thereby function in the prevention of osteoporosis. Several studies point to a positive effect of high protein intake on bone mineral density or content. This fact is associated with a significant reduction in hip fracture incidence, as recorded in a large prospective study carried out in a homogeneous cohort of postmenopausal women. Low protein intake (< 0.8 g/kg body weight/day) is often observed in patients with hip fractures and an intervention study indicates that following orthopedic management, protein supplementation attenuates post-fracture bone loss, tends to increase muscle strength, and reduces medical complications and rehabilitation hospital stay. There is no evidence that high protein intake per se would be detrimental for bone mass and strength. Nevertheless, it appears reasonable to avoid very high protein diets (i. e. more than 2.0 g/kg body weight/day) when associated with low calcium intake (i. e. less than 600 mg/day). In the elderly, taking into account the attenuated anabolic response to dietary protein with ageing, there is concern that the current dietary protein recommended allowance (RDA), as set at 0.8 g/kg body weight/day, might be too low for the primary and secondary prevention of fragility fractures.

Bonjour JP
Int J Vitam Nutr Res Mar 2011
PMID: 22139564

Protein Associated with Reduced Fractures

Abstract

Effects of meat consumption and vegetarian diet on risk of wrist fracture over 25 years in a cohort of peri- and postmenopausal women.

Evidence suggesting that a diet high in fruits and vegetables may be beneficial to bone health has sparked interest in the potential benefit of a vegetarian diet. However, other studies have raised a question regarding the adequacy of protein in such a diet.
The aim of the present study was to take a whole foods approach in examining the effects of foods high in protein on the risk of wrist fracture (WF) in a cohort with a significant proportion consuming a meat-free diet.
A cohort study of women who completed two lifestyle surveys 25 years apart.
One thousand eight hundred and sixty-five peri- and postmenopausal women at the time of the first survey.
There was a significant interaction between meat consumption and foods high in vegetable protein. Among vegetarians, those who consumed the least vegetable protein intake were at highest risk for fracture. However, increasing levels of plant-based high-protein foods decreased WF risk, with a 68% reduction in risk (hazard ratio (HR) = 0.32, 95% confidence interval (CI) 0.13-0.79) in the highest intake group. Among those with lowest vegetable protein consumption, increasing meat intake decreased the risk of WF, with the highest consumption decreasing risk by 80% (HR = 0.20, 95% CI 0.06-0.66).
The finding that higher consumption frequencies of foods rich in protein were associated with reduced WF supports the importance of adequate protein for bone health. The similarity in risk reduction by vegetable protein foods compared with meat intake suggests that adequate protein intake is attainable in a vegetarian diet.

Thorpe DL, Knutsen SF, Beeson WL, Rajaram S…
Public Health Nutr Jun 2008
PMID: 17686206

Protein Reduces Hip Fracture with Higher Intakes in Framingham Study

Abstract

Does dietary protein reduce hip fracture risk in elders? The Framingham Osteoporosis Study.

Association between dietary protein and fracture risk is unclear. We examined association between energy-adjusted protein intake and hip fracture risk in elders. The risk of hip fracture was reduced in upper quartiles of protein intake when compared with lowest quartile.
Studies of the association between dietary protein intake and hip fracture risk are conflicting. Therefore, we examined protein intake and hip fracture risk in a population-based group of elderly men and women.
Five hundred seventy-six women and 370 men from the Framingham Osteoporosis Study with no previous history of hip fracture completed Food Frequency Questionnaires. Energy-adjusted protein intake was evaluated as a continuous variable and as quartiles. Incidence rates and hazard ratios were calculated, adjusting for age, BMI, sex, and energy intake.
Among 946 participants (mean age 75 years), mean protein intake was found to be 68 gm/d. Increased protein intake was associated with a decreased risk of hip fracture compared to those in the lowest quartile of protein intake (Q2 HR = 0.70, Q3 HR = 0.56, and Q4 HR = 0.63; all p values ≥ 0.044), p for trend was 0.07. When a threshold effect was considered (Q2-4 vs Q1), intakes in the higher quartiles combined were associated with a significantly lower risk for hip fracture (HR = 0.63; p = 0.04).
Our results are consistent with reduced risk of hip fracture with higher dietary protein intake. Larger prospective studies are needed to confirm and extend this finding in elderly men and women.

Misra D, Berry SD, Broe KE, McLean RR…
Osteoporos Int Jan 2011
PMID: 20442986