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Journal of the American College of Nutrition, Vol. 25, No. 3, 170-177 (2006)
Published by the American College of Nutrition

Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis

Daniel Bunout, MD, Gladys Barrera, RN, Laura Leiva, Vivien Gattas, RD, María Pía de la Maza, MD, MSc, Ferdinand Haschke, MD, Philippe Steenhout, MD, Petra Klassen, PhD, Corinne Hager, PhD, Elizabeth Offord, MD and Sandra Hirsch, MD, MSc

INTA (D.B., G.B., L.L., V.G., M.P.d.l.M., S.H.)
Department of Medicine, Central Campus Faculty of Medicine (D.B.)
University of Chile, Santiago, CHILE, Nestec Ltd, Vevey, SWITZERLAND (F.H., P.S., P.K., C.H., E.O.)

Address correspondence to: Daniel Bunout MD, INTA University of Chile, PO Box 138-11, Santiago, CHILE. E-mail: dbunout{at}inta.cl


   ABSTRACT
TOP
 FOOTNOTES
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 REFERENCES
 
Objective: To study the effects of a special nutritional supplement on bone mineral density and bone turnover markers in Chilean elderly subjects with femoral osteoporosis.

Setting: Public primary health care clinics in Chile.

Subjects: Free living elderly subjects with femoral osteoporosis.

Interventions: Subjects were randomized to receive the usual nutritional supplement provided by the Chilean Ministry of Health or a special nutritional supplement providing, among other nutrients, 90 mg isoflavones, 800 mg calcium, 400 IU vitamin D, 60 ug vitamin K and 31 g proteins per day.

Measures of Outcome: At baseline, and after six and twelve months of supplementation, body composition, bone mineral density, serum 25 OH vitamin D, intact parathyroid hormone (iPTH), osteocalcin, decarboxylated osteocalcin, urinary aminoterminal telopeptide of type I collagen (NTX), deoxypyridoline cross links (Dpd) and equol were measured. Every month, urinary daidzein was measured in a morning urine sample.

Results: No differences between treatment groups were observed in body composition or bone mineral density changes. The group receiving the special supplement had a significant increase in serum 25 OH vitamin D and a significant decrease in serum iPTH and decarboxylated osteocalcin. No association between daidzein or equol excretion and changes in bone mineralization was observed.

Conclusions: A special supplement delivered to elderly subjects with osteoporosis improved serum vitamin D and reduced serum iPTH and undercarboxylated osteocalcin levels but did not affect BMD.

Key words: soy isoflavones, osteoporosis, bone turnover markers, elderly


   INTRODUCTION
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 REFERENCES
 
Osteoporosis and related fractures are a major public health problem, growing in importance as the population ages. Lifetime risk of fracture exceeds 40% for women and 13% for men. In the elderly, hip fractures are associated with a 20% mortality and great expenses in prostheses and long term nursing home care [1].

Nutritional risk factors are of particular importance to bone health because they are potentially modifiable. It is generally agreed that calcium and vitamin D are important nutrients for bone health, and supplements containing these nutrients are prescribed widely. Low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture. This vitamin promotes gamma-carboxylation of glutamyl residues of osteocalcin, reduces urinary calcium excretion and inhibits the production of bone reabsorbing agents, such as prostaglandin E2 and interleukin 6 [2]. Carboxylated osteocalcin has a higher affinity with hydroxyapatite in bone and enhances bone formation [3]. Supplementation with vitamin K reduces serum concentration of undercarboxylated osteocalcin [4], and reduces bone loss in postmenopausal women [5].

The use of soy phytoestrogens or dietary isoflavones is receiving increasing interest [6]. These weak estrogens can prevent bone loss in ovariectomized rats [7]. Several clinical trials in postmenopausal women showed that a supplement of approximately 90 mg/day of phytoestrogens, improves spine bone mineral density and reduces urinary excretion of bone resorption markers [8–13]. However, a recent large double blind randomized trial did not show any effect of 99 mg/day of isoflavones on bone health of postmenopausal women [14]. As expected, phytoestrogens do not have a beneficial effect in pre menopausal women, that maintain adequate endogenous estrogen production [15].

Most studies on bone health have been performed in postmenopausal women and there is less information on the value of nutritional supplements among osteoporotic elderly subjects. Therefore, the aim of this controlled trial was to study the effects of a high protein nutritional supplement enriched with calcium, vitamin D, K and phytoestrogens on bone mineral density and markers of bone metabolism in healthy elderly people, as compared with a standard nutritional supplement provided by the Chilean Ministry of Health.


   MATERIALS AND METHODS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 REFERENCES
 
Experimental Subjects
Healthy elderly subjects of both genders aged 70 years or more, living in the community of Santiago, Chile, were screened for the presence of femoral neck osteoporosis, as defined by WHO [16] (either less than 2.5 standard deviations of normal values for young people or less than 1 standard deviation of normal and a history of non traumatic fractures). Subjects with femoral osteoporosis were considered eligible if they were not taking medications that interfere with bone metabolism (glucocorticoids, estrogens, anticonvulsivants, anticoagulants, calcium, vitamin and mineral supplementation), did not suffer a fracture in the preceding six months, had a mini mental state examination (MMSE) [17] score of 19 or more, did not have any chronic or debilitating disease (such as cancer, renal or functional capacity II–III cardiac failure, the presence of chronic infections such as tuberculosis, connective tissue diseases or diabetes mellitus), had a mini nutritional assessment (MNA) [18] over 17 and signed a written informed consent. The study was approved by INTA’s ethics committee.

Eligible subjects were randomly assigned to receive a special nutritional supplement (SS) or to receive the standard nutritional supplement (MS), provided by the Chilean Ministry of Health to all elderly subjects aged 70 or more. The composition of both nutritional products is described in Table 1. Subjects were instructed to consume two servings of 58.5 g each, per day.


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  		Table 1. Nutritional Composition of the Products Delivered to the Elderly

 
At baseline, 6 months and 12 months of follow up, a full clinical assessment was done, body composition and bone mineral density were measured using a Lunar Prodigy double beam densitometer (Lunar Corporation, Madison Wisconsin, USA). The equipment was calibrated daily with an anthropometric phantom and all scans were read by the same trained operator to reduce the coefficient of variation. A fasting blood sample was drawn to measure routine blood chemistry (complete blood count, glucose, creatinine, urea nitrogen, total and HDL cholesterol, triglycerides, calcium and phosphorus), plasma intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (Vit D), osteocalcin and percentage of undercarboxylated osteocalcin. Subjects were requested to void a fasting second morning urine sample to measure calcium concentration, deoxypyridoline cross links (Dpd), aminoterminal telopeptide of type I collagen (NTX). On a further analysis, equol was measured also in these urine samples obtained at six and twelve months.

Every month, during one year of follow up, all subjects attended an outpatient clinic, where they were asked about adverse events, falls, adverse effects of the nutritional products and new medication use. A new supply of nutritional products was delivered and subjects returned the leftovers from the previous month. In each visit, subjects were requested to void and collect a second morning urine sample to measure daidzein.

Analytical Methods

  1. Clinical biochemistry and complete blood count were analyzed using routine automated methods at Laboratorio Vidaintegra SA.
  2. iPTH was measured by an immunoradiometric method using a commercial kit from Diagnostic Products Corporation (DPC, Los Angeles CA USA).
  3. Vit D was measured by a double antibody radioimmunoassay 125I RIA Kit DiaSorin (DiaSorin, Saluggia, Italy), following a previous extraction with acetonitrile.
  4. Osteocalcin was measured with an immunoradiometric method using a Osteo-RIACT kit from Cis Bio International (Saclay, France).
  5. Undercarboxylated osteocalcin was measured using an assay based on the low affinity of decarboxylated osteocalcin for hydroxyapatite [19]. In brief, 250 ul of serum were incubated with 7.5 mg hydroxyapatite in an Eppendorf tube for 1 h under constant agitation at 4°C and centrifuged afterwards at 2000 g at the same temperature. Undercarboxylated osteocalcin was measured with a Osteo-RIACT kit in the supernatant and was expressed as % of total osteocalcin.
  6. Total alkaline phosphatases were measured with a commercial kit from Química Clínica Aplicada (Amposta, Spain). This kit uses an optimized enzymatic method recommended by the Deutsche Gesellchaft für Klinische Chemie, DGKC).
  7. Urinary creatinine was measured using a commercial kit from Wiener Lab (Rosario, Argentina).
  8. Urinary Dpd was measured using a enzyme immunoassay commercial kit (METRA Dpd EIA) from Quidel (San Diego, CA, USA). Results were expressed as mmol Dpd/mmol creatinine.
  9. Urinary NTX was measured by an enzyme immunosorbent assay using an OSTEOMARK commercial kit from Ostex International Inc (Seattle, WA, USA).
  10. Urinary daidzein was measured by HPLC and diode array detection, using a modification of the technique described by Nurmy et al [20]. Briefly, samples were hydrolyzed with beta-glucuronidase, isoflavones were extracted with diethylether and injected to a Hypersil BDS C18 3µ column of 53 mm length (Alltech Associates INC, Deerfield Ill, USA).
  11. Urine for equol measurements was extracted in the same way as for daidzein. Equol was measured by HPLC and electrochemical detection, using a technique described by Gamache et al, with slight modifications [21].

Statistical Methods
Results are expressed as means ± standard deviations when a normal distribution was found or as median and range for data with non normal distribution. Correlations were calculated using the Pearson correlation coefficient. The effects of the SS on outcomes were evaluated with repeated measures two-way ANOVA, correcting data for covariables such as sex and age (for variables with a normal distribution) or Mann Whitney U test (for variables with a non normal distribution). Calculations were done on Statistica for Windows package version 5, Statsoft, Tulsa OK, USA.

Subjects that were lost to follow up, had experienced serious adverse events that precluded their maintenance in the protocol, had a fracture, took medications that could interfere with bone metabolism (calcium, vitamin D, oral corticosteroids, bisphosphonates, oral anticoagulants) or required a hospital admission for more than seven days during the study period, were excluded from the per protocol analysis of data.

The median value of urine daidzein excretion was calculated for each subject participating in the study.


   RESULTS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
REFERENCES
 
Eight hundred and eighty subjects were screened and 133 (15%) had a femoral neck osteoporosis. Of these, 100 fulfilled the inclusion criteria and were randomly allocated into one of two supplemented groups of 50 subjects each. The subject flow is depicted in Fig. 1. The initial demographic and laboratory values are shown in Table 2.


Figure 1
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  		Fig. 1. Patient flow during the follow up period.

 

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  		Table 2. Initial Demographic, Anthropometric and Laboratory Values in the Studied Patients (x ± Standard Deviation)

 
Compliance with the SS, according to the count of leftover sachets, was 82.8 ± 11.7%. Compliance with the MS was 71%, according to subject’s report on each clinic visit. During the follow up period, median daidzein excretion among subjects receiving the MS was 0. Among subjects on the SS, 32 subjects did excrete daidzein (median 300.5 ng/ml, range 10.7–2525.4 ng/ml) and 13 did not excrete daidzein. No association between daidzein excretion and compliance with the special supplement was observed.

During the follow up, no changes in body weight, arm, waist or hip circumferences were observed. No change in body composition, measured by DEXA, was observed in any group either. No differences between groups was observed for the evolution of bone mineral density in the spine or femoral neck (Table 3).


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  		Table 3. Evolution of Body Composition and Bone Mineral Density during Follow Up (x ± Standard Deviation)

 
The results of bone metabolism markers are shown in Table 4. Forty-eight (24 in each study group) subjects had plasma vit D levels below 16 ng/ml, considered the lower limit of normal. These levels were not influenced by the season in which basal values were obtained. At baseline, there was a significant negative correlation between vit D and iPTH (r = –0.33 p = 0.01). During follow up, vit D increased significantly in subjects receiving the SS. Among plasma bone turnover markers, total osteocalcin decreased in all groups and the decrease was more marked in subjects with the SS, but without reaching statistical significance. Undercarboxylated osteocalcin decreased significantly in patients receiving the SS, compared with subjects on the standard supplement. Likewise iPTH remained constant in individuals with the SS and increased in subjects with the MS. No significant changes were observed in plasma alkaline phosphatases. There was a wide variation in the urinary markers of bone resorption, and no differences were observed between treatment groups (Table 5).


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  		Table 4. Evolution of Serum Bone Turnover Markers during Follow Up (x ± Standard Deviation)

 

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  		Table 5. Evolution of Urine Bone Turnover Markers during Follow Up. Results Expressed as Median (range)

 
No association between daidzein excretion and changes in bone mineral density, were observed. At six and twelve months, 16 subjects receiving the SS had an equol excretion of more than 0.5 ug/ml (median 1.78 ug/ml range 0.51–10 ug/ml). No correlation between equol excretion and changes in bone mineral density were observed. Equol was not detected in any subject receiving the MS.

During follow up, subjects reported 72 episodes of falls (39 in subjects receiving the SS and 33 in the group with the MS). These falls resulted in three fractures, as stated in the patient flow (Fig. 1).


   DISCUSSION
 
In this prospective trial, we tested a special nutritional supplement, containing a higher amount of proteins, vitamins involved in bone formation and isoflavones on the bone health of osteoporotic elderly subjects. We observed improvements in several markers of bone formation and resorption.

We did not observe changes in bone mineral density in this study. However it must be borne in mind, that in the elderly, the rate of bone loss is less marked than in middle age subjects, specially among men [22]. Obviously, it is more difficult to observe an effect of an intervention, in subjects with less marked rates of bone mineral density change.

Bone turnover markers are good predictors for long term changes in bone mineral density [23] and risk of fractures [24,25]. Osteocalcin or bone-Gla protein is the most abundant noncollagenous protein of the bone matrix. All subjects in this study experienced a reduction in osteocalcin levels, that was more marked in subjects receiving the SS. This effect could be attributed in part to the isoflavone content of the SS, since other studies in rats and humans have shown that these compounds reduce osteocalcin levels [26,27].

Osteocalcin has a vitamin K dependent calcium-binding aminoacid, gamma carboxyglutamic acid at residues 17, 21 and 24. This aminoacid facilitates the binding of osteocalcin to hydroxyapatite in bone [28]. In our subjects, the SS significantly reduced the percentage of undercarboxylated osteocalcin. This effect of the supplement is probably due to its vitamin K content. The product provided 60 µg of vitamin K per day, an amount that has been reported to modify osteocalcin carboxylation [29].

Noteworthy was the high proportion of subjects with low vit D levels in our sample, that was not influenced by the season of the year in which the sample was obtained. As expected, there was a negative correlation between vit D and iPTH, indicating the state of secondary hyperparathyroidism [30]. Supplementation increased serum vit D and reduced iPTH. The SS had a higher content of vitamin D and calcium to ensure an adequate calcium retention. Most prospective supplementation studies with vitamin D and calcium show positive effects on bone mineral density and the incidence of fractures [31,32], although some authors have not found an effect on the latter [33]. Vitamin D supplementation may also decrease body sway and therefore reduce the risk of falls in the elderly [34]. However, we did not observe any effect of the supplement on the frequency of falls in our subjects. Vitamin D could also influence osteocalcin synthesis and therefore modify undercarboxylated osteocalcin levels [35,36]. Therefore, part of the effect of the supplement on undercarboxylated osteocalcin levels could be due to its vitamin D content. The great dispersion of NTX and Dpd values observed, similar to other reports [37], precludes a biological interpretation of this finding.

Recently, it has been proposed that responders to isoflavones are those who can convert daidzein to equol, i.e. the "equol producers". Indeed, in a 2 year clinical trial investigating the effect of soymilk consumption on bone health, equol producers showed the best response [38]. Based on these results, we further analyzed equol excretion on subjects receiving the special supplement. We found equol in urine at six or twelve months of follow up, in 36% of subjects receiving isoflavones. This figure is very similar to that reported by other authors [39]. However, we did not observe an association between equol excretion and changes in bone density or bone turnover markers.

The non specific effect of protein supplementation on bone turnover cannot be disregarded. Several cross sectional analyses show a positive association between protein intake and bone mineral density [40,41]. In a prospective study, performed in elderly subjects recovering from a hip fracture, Schurch reported that a protein supplement attenuated bone loss [42]. We also reported previously that total bone mineral density decreased less in patients receiving the MS, than in non supplemented controls [43]. Therefore, the higher protein content of the SS, could also have a positive effect on bone mineralization.

The SS had also a higher vitamin A content than the MS. Excess vitamin A ingestion is associated with a higher incidence of fractures [44]. However the amount of vitamin A in the SS was below the RDAs and more recent data shows that the association between vitamin A is U shaped. This indicates that both vitamin A deficiency and excess can increase the risk of fractures [45].

In summary, a special nutritional supplement, providing extra amounts of calcium, vitamin D, vitamin K and isoflavones, improved markers of bone turnover in osteoporotic elderly subjects.


   FOOTNOTES
TOP
 FOOTNOTES
ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 REFERENCES
 
Funded in part by Nestec Ltd., Vevey, Switzerland.

Received March 21, 2005. Accepted November 14, 2005.


   REFERENCES
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 REFERENCES
 

  1. Walker-Bone K, Dennison E, Cooper C: Epidemiology of osteoporosis.Rheum Dis Clin NA27 :1 –18,2001 .
  2. Feskanich D, Weber P, Willet WC, Rockett H, Booth SL, Colditz GA: Vitamin K intake and hip fractures in women: a prospective study.Am J Clin Nutr69 :74 –79,1999 .[Abstract/Free Full Text]
  3. Vermeer C, Gijsbers BL, Craciun AM, Groenen-van Dooren MM, Knapen MH: Effects of vitamin K on bone mass and bone metabolism.J Nutr126(4 Suppl) :1187S –1191S,1996 .
  4. Binkley NC, Krueger JA, Engelke JA, Foley AL, Suttie JW: Vitamin K supplementation reduces serum concentrations of under {gamma} carboxylated osteocalcin in healthy young and elderly adults.Am J Clin Nutr72 :1523 –1528,2000 .[Abstract/Free Full Text]
  5. Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C: Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.Calcif Tissue Int73 :21 –26,2003 .[Medline]
  6. Scheiber MD, Rebar RW: Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy?Menopause6 :233 –241,1999 .[Medline]
  7. Arjmandi BH, Birnbaum R, Goyal NV, Getlinger MJ, Juma S, Alekel L, Hasler CM, Drum ML, Hollis BW, Kukreja SC: Bone sparing effect of soy protein in ovarian hormone deficient rats is related to its isoflavone.Am J Clin Nutr68(6 Suppl) :1364S –1368S,1998 .
  8. Yamori Y, Moriguchi E, Teramoto T, Miura A, Fukui Y, Honda K, Fukui M, Nara Y, Taira K, Moriguchi Y: Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten week study.J Am Coll Nut21 :560 –563,2002 .[Abstract/Free Full Text]
  9. Morabito N, Crisafulli A, Vergara C, Gaudio A, Lasco A, Frisina N, D’Anna R, Corrado F, Pizzoleo MA, Cincotta M, Altavilla D, Ientile R, Squadrito F: Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study.J Bone Miner Res.17 :1904 –1912,2002 .[Medline]
  10. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr: Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.Am J Clin Nutr68(6 Suppl) :1375S –1379S,1998 .
  11. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T: Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women.Am J Clin Nutr72 :844 –852,2000 .[Abstract/Free Full Text]
  12. Chen YM, Ho SC, Lam SS, Ho SS, Woo JL: Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial.J Clin Endocrinol Metab88 :4740 –4747 .
  13. Atkinson C, Compston JE, Day NE, Dowsett M, Bingham SA: The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.Am J Clin Nutr79 :326 –333,2004 .[Abstract/Free Full Text]
  14. Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT: Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.JAMA292 :65 –74,2004 .[Abstract/Free Full Text]
  15. Anderson JJB, Chen X, Boass A, Symons M, Kohlmeier M, Renner JB, Garner SC: Soy isoflavones: no effects of bone mineral content and bone mineral density in healthy, menstruating young adult women after one year.J Am Coll Nutr21 :388 –393,2002 .[Abstract/Free Full Text]
  16. The World Health Organization (WHO) Study Group on Osteoporosis: "Assessment of Fracture Risk and its Application to Screening for Osteoporosis ." Geneva: World Health Organization,1994 .
  17. McDowell I, Newell C: "Measuring Health. A Guide to Rating Scales and Questionnaires ." New York: Oxford University Press,1996 .
  18. Vellas B, Garry PJ, Guigoz Y (eds):Mini Nutritional Assessment (MNA): Research and Practice in the Elderly. Nestle Nutrition Workshop Series, Clinical & Performance Programme ,Vol. 1 . Basel: Karger,1999 .
  19. Merle B, Delmas PD: Normal carboxylation of circulating osteocalcin (bone Gla-protein) in Paget’s disease of bone.Bone Miner11 :237 –245,1990 .[Medline]
  20. Tarja Nurmi T, Adlercreutz N: Sensitive high-performance liquid chromatographic method for profiling phytoestrogens using coulometric electrode array detection: application to plasma analysis.Anal Biochem274 :110 –117,1999 .[Medline]
  21. Gamache PH, Acworth IN: Analysis of phytoestrogens and polyphenols in plasma, tissue, and urine using HPLC with coulometric array detection.Proc Soc Exp Biol Med217 :274 –280,1998 .[Medline]
  22. Yoshimura N, Kinoshita H, Danjoh S, Takijiri T, Morioka S, Kasamatsu T, Sakata K, Hashimoto T: Bone loss at the lumbar spine and the proximal femur in a rural Japanese community, 1990–2000: the Miyama study.Osteoporos Int13 :803 –808,2002 .[Medline]
  23. Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB: Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.J Bone Miner Res13 :1431 –1438,1998 .[Medline]
  24. Woitge HW, Seibel M: Biochemical markers to survey bone turnover.Rheum Dis Clin North Am27 :49 –80,2001 .[Medline]
  25. Garnero P, Sornay-Rendu E, Claustrat B, Delmas P: Biochemical Markers of Bone Turnover, Endogenous Hormones and the Risk of Fractures in Postmenopausal Women: The OFELY Study.J Bone Miner Res15 :1526 –1536,2000 .[Medline]
  26. Picherit C, Bennetau-Pelissero C, Chanteranne B, Lebecque P, Davicco MJ, Barlet JP, Coxam V: Soybean isoflavones dose-dependently reduce bone turnover but do not reverse established osteopenia in adult ovariectomized rats.J Nutr131 :723 –728,2001 .[Abstract/Free Full Text]
  27. Mei J, Yeung SS, Kung AW: High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women.J Clin Endocrinol Metab86 :5217 –5221,2001 .[Abstract/Free Full Text]
  28. Gundberg CM, Nieman SD, Abrams S, Rosen H: Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin.J Clin Endocrinol Metab.83 :3258 –3266,1998 .[Abstract/Free Full Text]
  29. Binkley NC, Krueger DC, Kawahara TN, Engelke JA, Chappell RJ, Suttie JW: A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation.Am J Clin Nutr76 :1055 –1060,2002 .[Abstract/Free Full Text]
  30. Harris SS, Soteriades E, Dawson-Hughes B: Secondary hyperparathyroidism and bone turnover in elderly blacks and whites.J Clin Endocrinol Metab86 :3801 –3804,2001 .[Abstract/Free Full Text]
  31. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.New Engl J Med337 :670 –676,1997 .[Abstract/Free Full Text]
  32. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ: Vitamin D3 and calcium to prevent hip fractures in the elderly women.New Engl J Med327 :1637 –1642,1992 .[Abstract]
  33. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM: Vitamin D Supplementation and Fracture Incidence in Elderly Persons. A Randomized, Placebo-Controlled Clinical Trial.Ann Intern Med124 :400 –406,1996 .[Abstract/Free Full Text]
  34. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C: Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.J Bone Miner Res.15 :1113 –1118,2000 .[Medline]
  35. Paredes R, Gutierrez J, Gutierrez S, Allison L, Puchi M, Imschenetzky M, van Wijnen A, Lian J, Stein G, Stein J, Montecino M: Interaction of the 1alpha,25-dihydroxyvitamin D3 receptor at the distal promoter region of the bone-specific osteocalcin gene requires nucleosomal remodelling.Biochem J363 :667 –676,2002 .[Medline]
  36. Takahashi M, Naitou K, Ohishi T, Kushida K, Miura M: Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures.Clin Endocrinol (Oxf)54 :219 –224,2001 .[Medline]
  37. Tollin SR, Perlmutter S, Aloia JF: Serial Changes in Bone Mineral Density and Bone Turnover After Correction of Secondary Hyperparathyroidism in a Patient with Pseudohypoparathyroidism Type Ib.J Bone Mineral Res15 :1412 –1416,2000 .[Medline]
  38. Setchell KD, Brown NM, Lydeking-Olsen E: The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones.J Nutr132 :3577 –3584,2002 .[Abstract/Free Full Text]
  39. Setchell KD, Brown NM, Desai PB, Zimmer-Nechimias L, Wolfe B, Jakate AS, Creutzinger V, Heubi JE: Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.J Nutr133 :1027 –1035,2003 .[Abstract/Free Full Text]
  40. Rapuri PB, Gallagher JC, Haynatzka V: Protein intake: effects on bone mineral density and the rate of bone loss in elderly women.Am J Clin Nutr77 :1517 –1525,2003 .[Abstract/Free Full Text]
  41. Ilich JZ, Brownbill RA, Tamborini L: Bone and nutrition in elderly women: protein, energy, and calcium as main determinants of bone mineral density.Eur J Clin Nutr57 :554 –565,2003 .[Medline]
  42. Schürch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP: Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.Ann Intern Med128 :801 –809,1998 .[Abstract/Free Full Text]
  43. Bunout D, Barrera G, de la Maza P, Avendano M, Gattas V, Petermann M, Hirsch S: The impact of nutritional supplementation and resistance training on the health functioning of free-living Chilean elders: results of 18 months of follow-up.J Nutr131 :2441S –2446S,2001 .[Abstract/Free Full Text]
  44. Feskanich D, Singh V, Willett WC, Colditz GA: Vitamin A intake and hip fractures among postmenopausal women.JAMA287 :47 –54,2002 .[Abstract/Free Full Text]
  45. Opotowsky AR, Bilezikian JP: NHANES I follow-up study. Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study.Am J Med.117 :169 –174,2004 .[Medline]




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