Find a Practitioner
Herbs and Nutrients That May Assist
Soy
Glycine Max, pressed seed cake,dry
Hydroxyapatite
Calcium
Phosphorus
Vitamin C
Ascorbic acid
Boron
Borax (Sodium borate)
Zinc
Zinc amino acid chelate (Meta Zn ® - Zinc bisglycinate)
Manganese
Manganese amino acid chelate
Vitamin K
Phytomenadione
Vitamin D3
Colecalciferol
Actions
- Supports bone synthesis
- Promotes bone retention and prevents bone loss
- Supports bone preservation via selective oestrogen-receptor modulator (SERM) activity
Clinical Applications
- Healthy bone mineralisation, density and strength
- Bone loss in post-menopausal women
- Management of osteopenia and osteoporosis
Clinical Overview
Calcium is the primary mineral required for skeletal strength, [1] a deficiency of which is associated with a decline in bone mineral density (BMD) [Figure 1]. Progressive decline of BMD weakens the bones, leading to osteopenia (defined as mild to moderate bone loss) and osteoporosis (defined as severe bone loss) [2] and are associated with increased fracture risk, long-term morbidity and reduced quality of life. [3] Further, women are at a higher risk following menopause-associated decline in oestrogen levels, which increases the rate of bone catabolism. [4],[5] As such, a combination of highly-bioavailable microcrystalline hydroxyapatite calcium (MCHC) enriched with natural bone-growth factors, isoflavone-rich soy extract, and cofactors vitamin C, boron, zinc, manganese, vitamin K and vitamin D, offers an effective solution to mitigate calcium deficiency, reduce bone loss and support bone retention in individuals at risk of developing osteoporosis. [6]
Figure 1: Health-related factors that influence an individual’s risk of developing osteopenia and osteoporosis. [7],[8],[9],[10],[11],[12],[13],[14],[15]
Background Information
Osteoporosis is characterised by low BMD and microarchitectural deterioration of bone tissue [16] due to disturbances within bone modelling processes, namely:
- Increased bone resorption driven by osteoclasts (which initiate bone remodelling and removal of aged bone matrix); and,
- Decreased bone formation driven by osteoblasts (that synthesise new bone tissue). [17]
Normally, osteoclasts and osteoblasts regulate each other’s recruitment, differentiation and activity, balancing the remodelling process. [18] However, local and/or systemic alterations in hormones levels (including oestrogen and testosterone) or proinflammatory cytokines (which stimulate bone resorption) can shift this balance toward increased bone degradation, [19] resulting in reduced bone synthesis and low BMD. [20] This is further influenced by inadequate intakes of calcium and vitamin D, essential to the mineralisation of the extracellular matrix (ECM) that facilitates the structural integrity of bone architecture. [21]
Imbalances within healthy bone remodelling arise due to a combination of factors that accelerate BMD losses, leading to decreased bone strength and increased bone fragility. Poor clinical prognosis of osteopenia and osteoporosis is commonly associated with low calcium intake and is compounded by several other pathological drivers that diminish bone mass, such as:
- Hormonal changes that occur during menopause (i.e. low oestrogen levels), [22] or hypogonadism in males (i.e. low testosterone), [23] both of which negatively influence BMD;
- Vitamin D insufficiency (i.e. ≥50 and <75 nmol/l) and deficiency (<50 nmol/l), which negatively influences calcium absorption [24],[25];
- Low muscle mass and strength, which reduces mechanical loading in muscle that stimulates bone regeneration [26];
- Thyroid disease (i.e. hyperthyroidism), which increases bone turnover [27];
- Malabsorption (i.e. Coeliac disease), which negatively impacts calcium absorption and therefore bone strength [28];
- Smoking, which increases oxidative stress and levels of adrenal hormones (i.e. cortisol) that can reduce BMD [29];
- Alcohol intake (>10 standard drinks per week), which disrupts calcium homeostasis [30];
- Medications (i.e. glucocorticoids and proton pump inhibitors), which increase bone turnover and/or impairs calcium absorption [31];
- Hyperparathyroidism, which increases calcium liberation from bone [32]; and,
- Reduced kidney function with elevated dietary acid load, which may precipitate calcium leeching from bones. [33]
Of these factors, declining oestrogen levels following menopause is the most common driver of bone loss, [34] as oestrogen is involved in maintaining bone structure due to its regulatory effect on osteoclast apoptosis. [35] As such, in oestrogen deficient states, an osteoclast’s cellular lifespan is extended and is able to resorb more bone, resulting in a high-turnover state that leads to losses in bone mass. Therefore, in menopausal women at risk of developing osteopenia and osteoporosis, targeted nutritional strategies that modulate oestrogen activity can mitigate bone loss.
Clinically, BMD is used to diagnose osteopenia and osteoporosis, which is measured using axial skeleton screening by dual energy X-ray absorptiometry (DXA). This is reported as a T-score, indicated by variance in standard deviations (SDs) of the BMD measurement compared to the BMD of young healthy adults of the same sex. [36] The World Health Organisation (WHO) has defined osteoporosis and osteopenia based on T-score (Table 1). [37]
Table 1: WHO definitions of osteoporosis and osteopenia. [38]
|
T-score |
Interpretation |
Normal BMD |
–1.0 or above |
BMD not more than 1.0 SD below young adult mean |
Osteopenia |
–1.0 and –2.5 |
BMD between 1.0 and 2.5 SDs below young adult mean |
Osteoporosis |
–2.5 or below |
BMD 2.5 or more SDs below young adult mean |
In light of the above-mentioned influencing factors, medical guidelines support the use of holistic treatments for the management and prevention of osteoporosis. A routine approach recommended by the Royal Australian College of General Practitioners (RACGP) includes increasing weight-bearing exercise, maintaining a healthy diet, ensuring safe levels of sun exposure for adequate vitamin D, avoiding smoking and excessive alcohol intake, [39] as well as nutrient supplementation to promote healthy bone remodelling. Evidence supports the benefits of calcium, [40] vitamin D [41] and isoflavone-rich soy extracts [42] to prevent the progressive decline of T scores in patients, as outlined in the following clinical actions and applications.
Actions
Supports Bone Synthesis
To develop bone mass, the body requires a combination of calcium and nutritional cofactors to enable osteoblasts to form bone matrix. Calcium supports bone strength by building mass and density within skeletal microarchitecture, as well as facilitating repair mechanisms that maintain structural integrity. [43],[44] Calcium in the form of whole bone extract, MCHC, consists of bone-growth enhancing proteins (including ossein, osteocalcin, type 1 collagen, type I and II insulin growth factor [IGF-1 and IGF-2], and transforming growth factor-beta {TGF-β}), which promote the formation of organic bone matrix. [45],[46] MCHC also contains a blend of bone-building minerals including calcium, phosphorous, magnesium, potassium and zinc. [47],[48] Based on its unique properties and composition, MCHC mediates bone growth more effectively than conventional calcium supplements, such as calcium carbonate and calcium citrate. [49] Mechanisms attributed to MCHC’s bone-building effects include:
- Significantly increasing procollagen type I carboxy-terminal propeptide (PICP), [50] a downstream matrix-building protein produced by osteoblasts that forms 90% of bone matrix [51]; and
- Bone growth-factors, osteocalcin and collagen type I within MCHC, which stimulate osteoblast differentiation and proliferation. [52]
As a result, MCHC intake can support bone synthesis, as well as maintain adequate calcium intakes.
Vitamin C also promotes the generation of bone as an essential cofactor for collagen synthesis. The major amino acid constituents of collagen include glycine, proline, hydroxyproline and hydroxylysine. Specifically, vitamin C is a cofactor for prolyl hydroxylase and lysyl hydroxylase. These enzymes catalyse the hydroxylation of proline and lysine residues of procollagen, promoting the proper folding of the stable collagen triple-helix conformation. [53] As a primary structural protein, collagen constitutes a significant proportion of the body’s protein matrix required for the growth, as well as the repair and maintenance of muscle, connective tissue and bone. [54] Boron contributes to bone mineralisation by promoting messenger ribonucleic acid (mRNA) osteoblastic cell expression, thereby accelerating osteoblast activity [55],[56]; complimenting the effects of MCHC.
Further to this, zinc increases bone growth factors and bone matrix proteins, which are involved in the stimulation of bone formation and proliferation of osteoblastic cells. Zinc modulates the anabolic effect of IGF-1 in osteoblasts, enhancing the synthesis of bone matrix and, therefore, bone strength. [57] Based on the abundance of zinc in bone tissue (approximately 30% of all body stores), zinc is considered a key nutritional cofactor for the maintenance of bone strength. [58]
Manganese is another essential element involved in the formation of bone. [59] It is required for the biosynthesis of glycosaminoglycans, which are polysaccharide compounds that form connective tissue and enhance bone matrix formation. Manganese acts as a cofactor for several enzymes in bone, [60] namely glycosyl transferases that promote cartilage regeneration and healthy bone mineralisation. [61] Furthermore, vitamin K1 (phylloquinone) plays a key role in many physiological processes including bone mineralisation via the stimulation of gamma-carboxylation enzymes. These, in turn, activate vitamin K-dependant proteins, osteocalcin and matrix Gla (MGP), involved in bone matrix synthesis (Figure 2). [62]
Figure 2: Mechanisms of action of vitamin K-dependent proteins in bone. [63]
Key: cOC: Carboxylated osteocalcin; ucOC: Undercarboxylated osteocalcin; ucMGP: Undercarboxylated matrix Gla protein; cMGP: Carboxylated matrix Gla protein; NF-kB: Nuclear factor kB; SXR: Steroid and xenobiotic receptor; RANKL: Receptor activator of nuclear kappa B ligand; RANK: Receptor activator of nuclear kappa B; ECM: Extracellular matrix.
Additionally, vitamin D acts to promote the intestinal absorption of calcium and phosphate, and enhances the renal reabsorption of calcium. [64],[65] Adequate vitamin D therefore supports calcium absorption and facilitates the accrual of bone mass.
Promotes Bone Retention and Prevents Bone Loss
After peak bone mass is reached in early adulthood, skeletal strength and BMD are negatively affected by persistent low calcium intakes, changes to calcium absorption and excretion, or as a result of ageing. In menopausal women and men aged 55 years, bone balance naturally becomes negative, with bone loss at skeletal sites correlating with calcium losses of approximately 15 g per year. [66] This is exacerbated by states of chronic calcium deficiency due to habitual inadequate intake, poor absorption or vitamin D deficiency. This causes the mineral balance to shift, stimulating the extraction of calcium from bone stores at the expense of bone mass, in order to maintain circulating calcium. [67] As such, in older adults, adequate calcium intake promotes calcium storage within skeletal tissues and facilitates the retention of bone mass.
In post-menopausal women, research has shown calcium supplementation to be more effective than placebo in reducing bone loss in the second year of supplementation. [68] In this population group, MCHC has shown greater efficacy and tolerability over calcium carbonate for the prevention of BMD decline. [69] Specific mechanisms associated with the ability of MCHC to support bone mass retention [70] include:
- Decreasing bone resorption by delaying the development of precursor bone-remodelling cells, osteoclasts, involved in the remodelling and removal of aged bone matrix [71]; and,
- Moderating the activity of bone turnover enzyme, C-terminal telopeptide of type 1 collagen (CTX). [72]
The combination of boron and hydroxyapatite observed in in vitro studies on human cell lines has been demonstrated to influence signalling pathways involved in osteogenic differentiation within mesenchymal cells (MSCs), also known as stem cells, [73] promoting skeletal retention and bone matrix synthesis. [74] Additionally, vitamin K-dependant proteins, osteocalcin and matrix Gla (MGP), promote bone matrix synthesis within skeletal sites, thereby supporting bone regeneration and retention. [75], [76] Further, vitamin D promotes healthy bone remodelling on osteoblasts and osteoclasts [77], as well as maintaining dietary and supplemental calcium absorption. [78],[79] As such, adequate vitamin D in combination with calcium and other nutritional cofactors prevents the acceleration of net BMD losses that may increase the risk of osteopenia and osteoporosis.
Supports Bone Preservation via Selective Oestrogen-Receptor Modulator (SERM) Activity
Natural polyphenol compounds have been documented act as selective oestrogen receptor modulators (SERMs) that exert mild oestrogenic effects on hormone-sensitive processes (such as osteoclast activity); shown to assist with bone-preservation in menopausal women. [80] Particularly, polyphenols within Glycine max (soy), including genistein, daidzein and glycitein, are biologically similar to endogenous oestrogen, specifically 17-β-oestradiol, and possess the ability to interact with oestrogen receptors (ERs) throughout the body. [81] Glycine max extract contains a minimum of 40% isoflavones shown to inhibit osteoclast proliferation and decrease bone resorption by osteoclasts. [82]
As such, soy isoflavones are considered SERMs that mimic the activity of oestrogen. [83],[84],[85] These compounds can prevent BMD losses in oestrogen-deficient states [86] and offset bone loss that occurs after menopause; appropriate for use in patients with postmenopausal osteopenia or osteoporosis who are unable to tolerate or are seeking an adjunct to oestrogen and/or bisphosphonate therapies. [87]
Clinical Applications
Healthy Bone Mineralisation, Density and Strength
The bone-strengthening effects of calcium and vitamin D has been demonstrated in a randomised, double-blind, placebo-controlled trial examining the effects of 1,890 mg/d to 2,246 mg/d of calcium and 938 IU/d to 1,036 IU/d of vitamin D over 12 weeks. [88] Participants aged 18 to 42 years, undergoing rigorous military training, received calcium and vitamin D-enriched food bars (n=71) or placebo (n=76), and were assessed for calcium intakes before and after the study. Patients were further evaluated for markers of bone turnover, changes in BMD via peripheral quantitative computed tomography (pQCT) and bone strength index (BSI).
Findings in the treatment group revealed in the context of adequate calcium intake and increased vitamin D intake, markers of bone turnover (i.e. bone catabolism) were decreased (osteocalcin, bone-specific alkaline phosphatase and tartrate-resistant alkaline phosphatase [p<0.05]). While increases in BSI were associated with physical training independent of calcium and vitamin D supplementation, it was observed that participants in the treatment group with low baseline levels of vitamin D experienced the greatest BSI improvement (p<0.001); indicating the positive relationship between vitamin D intake and bone strength in response to calcium supplementation. [89]
Compelling results have been demonstrated in another randomised, double-blind, placebo-controlled trial in 197 male and female participants subject to military training, consuming 2,064 mg/d of calcium carbonate and 1,092 IU/d of vitamin D over nine weeks. [90] The treatment group, who achieved adequate calcium intakes compared to the placebo group, experienced an increase in circulating calcium levels (p<0.02), maintained parathyroid titres (which normally rise with low calcium intake [p<0.032]) and reduced the rate of bone resorption (p<0.006); evidencing the positive effects of nutritional therapy on calcium status and bone health. [91] Further, in a randomised, double-blind, placebo-controlled study conducted over six months in young healthy male athletes (n=17, aged 20.18 ± 3.23), 800 mg/d of calcium carbonate in addition to 400 IU/d vitamin D increased serum vitamin D levels and reduced markers of bone turnover (CTX), thereby facilitating healthy bone mass. [92]
In addition to this, vitamin K status in prepubescent girls has been associated with increased bone mineral content, [93] endorsing the role of vitamin K as a cofactor in the development of bone strength during childhood. Collectively, these findings validate the positive effects of adequate calcium, vitamin D and vitamin K intake relative to bone strength.
Bone Loss in Post-Menopausal Women
A meta-analysis including data from 1,240 menopausal women demonstrated that 82 mg/d of soy isoflavones supplemented for 6 to 12 months significantly increased spine BMD by an average of 2.38% (p<0.001) compared to controls. [94] This effect was partially attributed to individual gut microbiota, shown to enhance the conversion of soy compounds (i.e. daidzein) to its active form, equol, which selectively stimulates ER-β receptors. [95] Interestingly, in a blinded randomised cross-over intervention trial, 24 postmenopausal women were pre-screened for their ability to convert daidzein to equol to determine if this influenced treatment outcomes. Positive effects were observed in patients who consumed adequate dietary calcium before soy isoflavone supplementation (with dosages ranging between 54 mg/d to 220mg/d) for a duration of 50 days followed by a 50-day wash-out period.
Further outcomes of the study revealed that active isoflavone supplementation over a total of 250 days increased bone calcium retention by 3.4% to 7.6% (p<0.05). [96] The most-effective intervention delivered 105.23 mg/d of total isoflavones as genistein, daidzein, and glycitein, and was found to increase bone calcium retention by 7.6% (p<0.0001). Moreover, there was no difference in bone calcium retention between equol producers and non-producers (p=0.5), supporting the benefits of isoflavone-rich soy extracts in postmenopausal women irrespective of gut microbiota functionality. [97]
Similarly, in a randomised, placebo-controlled trial in 99 postmenopausal women (n=48), 50 mg/d of soy isoflavones over 12 months was shown to decrease bone metabolism markers, with a significant increase in estimated bone mineral density (p<.04). [98] Comparable outcomes were also observed in a randomised, double-blind, placebo-controlled trial examining the effects of placebo (n=61) compared to 80 mg/d (n=56) or 120 mg/d (n=56) of soy isoflavones over three years on postmenopausal volumetric BMD. [99] Results indicated that 120 mg/d of soy isoflavones were protective of cortical femur BMD [100]; supporting the positive effects of soy isoflavones for the progressive bone mass decline following menopause.
Clinical data outlines the efficacy of MCHC over calcium carbonate to prevent BMD losses based on the outcomes of a prospective, open-label controlled trial in 1,032 menopausal women with normal BMD or slight osteopenia. [101] Women in the study were assigned either 712 mg/d of MCHC or 1,000 mg/d of calcium carbonate for three years and were assessed for BMD with dual energy X-ray absorptiometry (DXA) [*] at baseline, 18 months and after the trial (i.e. 36 months). Women treated with MCHC maintained BMD scores (mean T-score increase of 0.01 [±0.82]), however women in the calcium carbonate group experienced BMD decline (mean T-score decrease of -0.23 [±0.76]), indicating superior efficacy of MCHC compared to calcium carbonate (p<0.01). Additional benefits included better tolerability profile of MCHC compared to calcium carbonate resulting in less digestive issues.
Moreover, findings from a prospective, comparative, non-randomised open-label study in 851 perimenopause women with a DXA T score of -2 revealed MCHC to exert positive effects on BMD retention. [102] In this trial, 712 mg/d of MCHC over three years was shown to stabilise BMD at lumbar vertebrae sites, L2 and L4 (i.e. -0.03% loss), compared to -3.1% regression observed in the calcium carbonate group (1,000 mg/d) [p<0.001] {Figure 3}. [103] Based on these outcomes, researchers concluded that the greater benefits of MCHC could be attributed with the presence of bone growth factors that enhance bone matrix formation, thereby preventing BMD decline associated with menopause. [104],[105]
Figure 3: Lumbar T score changes (mean) from baseline within L2 and L4 vertebrae. [106]
Further supporting the protective effects of MCHC, outcomes of a four-year retrospective follow-up study in 112 post-menopausal women aged 45 to 55 years receiving high doses of MCHC (3,320 mg/d) revealed that supplementation could revert osteopenic DXA scores. [107] In this trial, baseline trabecular BMD T and Z scores[†] were -1.27 ± 0.7 and -1.03 ± 0.7 respectively, which improved to -0.86 ± 0.7 and -0.62± 0.7 after four years (p<0.0001). This finding suggests that MCHC provides an effective and safe strategy to protect bone mass in menopausal women. [108]
Management of Osteopenia and Osteoporosis
In patients with osteopenic T scores (i.e. >-2), the likelihood of developing osteoporosis and fracture risk is high. [109] As such, preserving bone strength is a key goal of managing osteopenia and osteoporosis to mitigate fracture risk.
MCHC has been demonstrated to reduce the rate of bone loss in osteoporosis more effectively than calcium carbonate. [110] In a randomised, open-label, parallel-group, controlled study in osteoporotic women (n= 54), MCHC was more effective in lowering progressive BMD loss over three years. In this study, 712 mg/d elemental calcium (in the form of MCHC) paired with 266 µg/d (10,640 IU) of vitamin D retained lumbar spine mass more effectively than 1,000 mg/d of elemental calcium from calcium carbonate with the same dose of vitamin D (-1.1% vs. -2.3% loss; p<0.05; Figure 4). Further, researchers identified a non-significant trend in increased femoral neck mass in both groups, however this outcome was more pronounced in the MCHC group, suggesting positive benefits of MCHC on skeletal health.
Figure 4: Changes in mean BMD at the lumbar spine. [111]
Further reinforcing these findings are outcomes from a meta-analysis of six high-quality, randomised, controlled clinical trials in patients with a clinical diagnosis of osteopenia, osteoporosis risk factors or osteoporosis. [112] In this study, it was determined that MCHC exerted a greater effect on bone mass retention compared to calcium carbonate, thereby limiting bone loss and reducing the progression of osteoporosis. [113]
Additional benefits of MCHC have been observed in combination with oestrogen-agonist medication, raloxifene, in preventing bone loss compared to calcium carbonate. In a randomised, open-label clinical trial in 90 osteopenic and osteoporotic women (baseline T scores -2.29), 712 mg/d of MCHC over three years was shown to prevent losses in bone mass more effectively than calcium carbonate (-18.72 m/s in the MCHC group vs. -63.64 m/s in the calcium carbonate group; p<0.006). [114] This supports the protective effect of MCHC combined with pharmaceutical medication to minimise progressive bone loss in osteoporosis.
Another interesting application of MCHC is its ability to mitigate bone losses associated with corticosteroids. Two separate studies have observed the protective effects of MCHC on steroid-induced decline in BMD. In a randomised, controlled clinical trial, 37 patients were prescribed prednisolone at variable doses between 5 mg/d and 20 mg/d to manage conditions such as bronchial asthma in combination with 6 g/d to 8 g/d of MCHC over 12 months. [115] Results indicated that patients in the control group (n=7) experienced greater decreases in cortical bone thickness over 12 months compared to the treatment group (n=18) [i.e. -0.27 mm loss in controls vs. - 0.01mm in the treatment group] reported to reach near statistical significance in the small population sample. [116]
In addition to this, in a randomised-controlled trial, conducted in patients receiving 5 mg/d to 12.5 mg/d of prednisolone for the treatment of hepatitis, 8 g/d of MCHC administered over two years was observed to prevent progressive losses within trabecular bone volume compared to controls (p<0.025); indicating the protective effect of MCHC in mitigating medication-induced osteopenia and osteoporosis. [117]
As outlined previously, vitamin D works via multiple mechanisms to assist with BMD retention in osteopenia and osteoporosis, as supported by a large body of evidence. For instance, in a systematic review, vitamin D supplementation between 700 IU/d to 800 IU/d was shown to reduce the risk of hip and nonvertebral fractures in ambulatory or institutionalised elderly persons compared to 400 IU/d. [118] Further, 800 IU/d of vitamin D combined with calcium may decrease the incidence of non-vertebral fractures by 10% to 20% in older individuals with lower baseline vitamin D, [119] supporting the importance of maintaining adequate vitamin D to mitigate fracture risk.
The combination of MCHC, soy isoflavones, vitamin C, boron, zinc, manganese, vitamin K1 and vitamin D with bone-matrix enhancing growth factors can be used to strengthen bone health across the lifespan, limit BMD losses, maintain skeletal health during menopause, slow the progression of osteopenia and osteoporosis, and limit the negative effects of long-term corticosteroid use that accelerate BMD losses.
Safety Information
Disclaimer: In the interest of supporting health Practitioners, all safety information provided at the time of publishing (XXX 2025) has been checked against authoritative sources. Please note that not all interactions have been listed.
For further information on specific interactions with health conditions and medications, refer to clinical support on 1800 777 648(AU), 0508 227 744(NZ) or via email, anz_clinicalsupport@metagenics.com, or via Live Chat www.metagenics.com.au, www.metagenics.co.nz
Pregnancy
Breastfeeding
Prescribing Tips and Notes
- Effects of soy on thyroid function: The potential goitrogenic action of soy may be largely attributed to in vitro and animal studies, and the direct extrapolation of animal research specific to thyroid function is discordant with human thyroid function. [120],[121],[122] A review of 14 human clinical studies provided little evidence that soy protein or isoflavones exert anti-thyroid effects in healthy subjects. [123] These results are consistent with a report by the European Food Safety Authorty (EFSA), which concluded consumption of soy isoflavones between 40 mg to 200 mg daily for up to three years does not influence thyroid function in healthy women. [124] Since there is evidence to suggest an inhibitory effect on thyroxine synthesis in the absence of iodine, it is reasonable to ensure patients ingesting soy foods and supplements consume adequate iodine, particularly patients with subclinical hypothyroidism. However, for the most part, dietary soy is unlikely to have a detrimental impact on thyroid function. [125],[126]
- Use of soy with Tamoxifen and other selective oestrogen receptor modulators: Diets high in soy, such as traditional Asian diets, are associated with less oestrogen-dominant conditions, such as breast, prostate and endometrial cancers. [127] Soy isoflavones are known as natural selective oestrogen receptor modulators (SERMs) – similar to medications used for breast cancer treatment and prevention, tamoxifen and raloxifene. [128] Thus, while structurally similar, isoflavones do not exert effects equal to the hormone oestrogen. [129],[130],[131] A large prospective study in women receiving tamoxifen therapy found that soy isoflavone consumption, at levels comparable to those in typical Asian diets, may actually decrease the chance of cancer reoccurrence in women, and most importantly, soy did not interfere with tamoxifen efficacy. [132]
Contraindications
Cautions
Footnotes
[*] BMD is typically measured by axial skeleton screening by dual energy X-ray absorptiometry (DXA). This is reported as a T-score, indicated by variance in standard deviations (SDs) of the BMD measurement compared to the BMD of young healthy adults of the same sex. Normal BMD: T-score –1.0 or above, Osteopenia: T-score between –1.0 and –2.5, Osteoporosis: T-score –2.5 or below. This may also be reported as a Z score, which compares BMD to that of adults of the same age
References
[1] Chandran M, Tay D, Mithal A. Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health. Aging Clin Exp Res. 2019 Jun;31(6):765-781. doi: 10.1007/s40520-019-01150-5.
[2] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[3] Abimanyi-Ochom J, Watts JJ, Borgström F, Nicholson GC, Shore-Lorenti C, Stuart AL, et al. Changes in quality of life associated with fragility fractures: Australian arm of the international cost and utility related to osteoporotic fractures study (AusICUROS). Osteoporos Int. 2015 Jun;26(6):1781-90. doi: 10.1007/s00198-015-3088-z.
[4] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[5] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[6] Health and Medical Research Council. Nutrient reference values for Australia and New Zealand. Calcium [Internet]. Canberra (ACT): Australian Government. 2017 September [cited 2020 Nov 3]. Available from: https://www.nrv.gov.au/nutrients/calcium.
[7] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[8] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[9] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
[10] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[11] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[12] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[13] Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health. Clin Sci (Lond). 2007 Sep;113(5):233-41. doi: 10.1042/CS20060173.
[14] Kogawa M, Wada S. Osteoporosis and alcohol intake. Clin Calcium. 2005 Jan;15(1):102-5. PMID: 15632479.
[15] Wynn E, Lanham-New SA, Krieg MA, Whittamore DR, Burckhardt P. Low estimates of dietary acid load are positively associated with bone ultrasound in women older than 75 years of age with a lifetime fracture. J Nutr. 2008 Jul;138(7):1349-54. doi: 10.1093/jn/138.7.1349.
[16] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx..
[17] Jameson JL, De Groot LJ, Kretser DM, Giudice LC, Grossman AB, Melmed S, et al. Endocrinology: adult and pediatric. 7 th Ed. Philadelphia (USA): Elsevier/Saunders; 2016. p. 1038-1062.
[18] Jameson JL, De Groot LJ, Kretser DM, Giudice LC, Grossman AB, Melmed S, et al. Endocrinology: adult and pediatric. 7 th Ed. Philadelphia (USA): Elsevier/Saunders; 2016. p. 1038-1062.
[19] Jameson JL, De Groot LJ, Kretser DM, Giudice LC, Grossman AB, Melmed S, et al. Endocrinology: adult and pediatric. 7 th Ed. Philadelphia (USA): Elsevier/Saunders; 2016. p. 1038-1062.
[20] Jameson JL, De Groot LJ, Kretser DM, Giudice LC, Grossman AB, Melmed S, et al. Endocrinology: adult and pediatric. 7 th Ed. Philadelphia (USA): Elsevier/Saunders; 2016. p. 1038-1062.
[21] Health and Medical Research Council. Nutrient reference values for Australia and New Zealand. Calcium [Internet]. Canberra (ACT): Australian Government. 2017 September [cited 2020 Nov 3]. Available from: https://www.nrv.gov.au/nutrients/calcium.
[22] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[23] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[24] Liu X, Baylin A, Levy PD. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br J Nutr. 2018 Apr;119(8):928-936. doi: 10.1017/S0007114518000491.
[25] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[26] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
[27] Baumgartner C, Blum MR, Rodondi N. Swiss Med Wkly. 2014 Dec 23;144:w14058; Juby AG, Hanly MG, Lukaczer D. Maturitas. 2016 May;87:72-8; Ladenson PW, Singer PA, Ain KB, et al. Arch Intern Med. 2000 Jun 12;160(11):1573-5.
[28] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[29] Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health. Clin Sci (Lond). 2007 Sep;113(5):233-41. doi: 10.1042/CS20060173.
[30] Kogawa M, Wada S. Osteoporosis and alcohol intake. Clin Calcium. 2005 Jan;15(1):102-5. PMID: 15632479.
[31] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx..
[32] Ferri FF. Ferri’s clinical advisor 2020. Philadelphia (USA): Elsevier/Churchill Livingstone; 2020. p. 729-731.
[33] Wynn E, Lanham-New SA, Krieg MA, Whittamore DR, Burckhardt P. Low estimates of dietary acid load are positively associated with bone ultrasound in women older than 75 years of age with a lifetime fracture. J Nutr. 2008 Jul;138(7):1349-54. doi: 10.1093/jn/138.7.1349.
[34] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[35] Elsevier Clinical Key. Osteoporosis [Internet]. Melbourne (AUS): Elsevier; 2018 [updated Nov 7 2018; cited 2020 Jul 21]. Available from https://www.clinicalkey.com.au. subscription required to view.
[36] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[37] Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994 Nov;4(6):368-81. doi: 10.1007/BF01622200.
[38] Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994 Nov;4(6):368-81. doi: 10.1007/BF01622200.
[39] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[40] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
[41] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
[42] Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42. PMID: 20199985.
[43] Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3.
[44] Australian Bureau of Statistics. Australian Health Survey: Nutrition First Results - Foods and Nutrients 2011-12: Calcium [Internet]. Canberra (ACT): Australian Bureau of Statistics; 2015 Mar 6 [cited 2020 Feb 7]. Available from: https://www.abs.gov.au/statistics/health/health-conditions-and-risks/australian-health-survey-usual-nutrient-intakes/latest-release.
[45] Korzh M, Dedukh N. Application of ossein-hydroxyapatite complex for osteoporosis and fracture treatment. Orthopaed Traumatol Prosthet. 2016(2):120-9.
[46] Castelo-Branco C, Dávila Guardia J. Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review. Climacteric. 2015 Feb;18(1):29-37. doi: 10.3109/13697137.2014.929107.
[47] Korzh M, Dedukh N. Application of ossein-hydroxyapatite complex for osteoporosis and fracture treatment. Orthopaed Traumatol Prosthet. 2016(2):120-9.
[48] Castelo-Branco C, Dávila Guardia J. Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review. Climacteric. 2015 Feb;18(1):29-37. doi: 10.3109/13697137.2014.929107.
[49] Castelo-Branco C, Dávila Guardia J. Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review. Climacteric. 2015 Feb;18(1):29-37. doi: 10.3109/13697137.2014.929107.
[50] Srimongkol T, Bunyaratavej N. Clinical study of efficacy of hydroxyapatite. J Med Assoc Thai. 2005 Oct;88 Suppl 5:S24-6. PMID: 16869103.
[51] Eastell R, Hannon RA. Biochemical markers of bone turnover [Internet]. New York: Academic Press; 2007. p. 337–349. doi:10.1016/b978-012369443-0/50034-x
[52] Korzh M, Dedukh N. Application of ossein-hydroxyapatite complex for osteoporosis and fracture treatment. Orthopaed Traumatol Prosthet. 2016(2):120-9.
[53] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 549.
[54] Byrd-Bredbenner C, Wardlaw GM. Wardlaw's Perspectives in nutrition. 8th ed., International student ed. Dubuque, IA: McGraw-Hill, 2009:233,241-2.
[55] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 749.
[56] Khaliq H, Juming Z, Ke-Mei P. The physiological role of boron on health. Biol Trace Elem Res. 2018 Nov;186(1):31-51. doi: 10.1007/s12011-018-1284-3.
[57] Rico H, Villa LF. Zinc, a new coherent therapy for osteoporosis? Calcif Tissue Int. 2000;67(5):422-3.
[58] Suzuki T, Katsumata S, Matsuzaki H, Suzuki K. Dietary zinc supplementation increased TNFα and IL1β-induced RANKL expression, resulting in a decrease in bone mineral density in rats. J Clin Biochem Nutr. 2016 Jan;58(1):48-55. doi: 10.3164/jcbn.15-71.
[59] Health and Medical Research Council. Nutrient reference values for Australia and New Zealand. Manganese [Internet]. Canberra (ACT): Australian Government. 2017 September [cited 2020 Nov 12]. Available from: https://www.nrv.gov.au/nutrients/manganese.
[60] Rico H, Villa LF. Zinc, a new coherent therapy for osteoporosis? Calcif Tissue Int. 2000;67(5):422-3.
[61] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 749.
[62] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 509.
[63] Palermo A, Tuccinardi D, D’Onofrio L, Watanabe M, Maggi D, Maurizi AR, et al. Vitamin K and osteoporosis: Myth or reality? Metabolism. 2017 May;70:57-71. doi: 10.1016/j.metabol.2017.01.032.
[64] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 478.
[65] van Driel M, van Leeuwen JPTM. Vitamin D endocrinology of bone mineralization. Mol Cell Endocrinol. 2017 Sep 15;453:46-51. doi: 10.1016/j.mce.2017.06.008.
[66] Chandran M, Tay D, Mithal A. Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health. Aging Clin Exp Res. 2019 Jun;31(6):765-781. doi: 10.1007/s40520-019-01150-5.
[67] Chandran M, Tay D, Mithal A. Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health. Aging Clin Exp Res. 2019 Jun;31(6):765-781. doi: 10.1007/s40520-019-01150-5.
[68] Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, et al.; Osteoporosis Methodology Group; Osteoporosis Research Advisory Group. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev. 2004;(1):CD004526. doi: 10.1002/14651858.CD004526.pub2.
[69] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[70] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[71] Castelo-Branco C, Dávila Guardia J. Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review. Climacteric. 2015 Feb;18(1):29-37. doi: 10.3109/13697137.2014.929107.
[72] Srimongkol T, Bunyaratavej N. Clinical study of efficacy of hydroxyapatite. J Med Assoc Thai. 2005 Oct;88 Suppl 5:S24-6. PMID: 16869103.
[73] Gizer M, Köse S, Karaosmanoglu B, Taskiran EZ, Berkkan A, Timuçin M, et al. The effect of boron-containing nano-hydroxyapatite on bone cells. Biol Trace Elem Res. 2020 Feb;193(2):364-376. doi: 10.1007/s12011-019-01710-w.
[74] Valenti MT, Dalle Carbonare L, Mottes M. Osteogenic differentiation in healthy and pathological conditions. Int J Mol Sci. 2016 Dec 27;18(1):41. doi: 10.3390/ijms18010041.
[75] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 509.
[76] Palermo A, Tuccinardi D, D’Onofrio L, Watanabe M, Maggi D, Maurizi AR, et al. Vitamin K and osteoporosis: Myth or reality? Metabolism. 2017 May;70:57-71. doi: 10.1016/j.metabol.2017.01.032.
[77] Laird E, Ward M, McSorley E, Strain JJ, Wallace J. Vitamin D and bone health: potential mechanisms. Nutrients. 2010 Jul;2(7):693-724. doi: 10.3390/nu2070693.
[78] Kohlmeier, M. Nutrient metabolism. Amsterdam: Academic Press; 2003. p. 478.
[79] van Driel M, van Leeuwen JPTM. Vitamin D endocrinology of bone mineralization. Mol Cell Endocrinol. 2017 Sep 15;453:46-51. doi: 10.1016/j.mce.2017.06.008.
[80] Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42. PMID: 20199985.
[81] Zaheer K, Humayoun AM. An updated review of dietary isoflavones: nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr. 2017 Apr 13;57(6):1280-1293. doi: 10.1080/10408398.2014.989958.
[82] Chang KL, Hu YC, Hsieh BS, Cheng HL, Hsu HW, Huang LW, et al. Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized rats. Nutrition. 2013 Jan;29(1):250-7. doi: 10.1016/j.nut.2012.03.009.
[83] Zaheer K, Humayoun AM. An updated review of dietary isoflavones: nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr. 2017 Apr 13;57(6):1280-1293. doi: 10.1080/10408398.2014.989958.
[84] Messina M. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients. 2016 Nov;8(12):1-42.
[85] Rizzo G, Baroni L. Soy, soy foods and their role in vegetarian diets. Nutrients. 2018 Jan 5;10(1):43. doi:10.3390/nu10010043.
[86] Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42. PMID: 20199985.
[87] Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42. PMID: 20199985.
[88] Gaffney-Stomberg E, Nakayama AT, Guerriere KI, Lutz LJ, Walker LA, Staab JS, et al. Calcium and vitamin D supplementation and bone health in Marine recruits: Effect of season. Bone. 2019 Jun;123:224-233. doi: 10.1016/j.bone.2019.03.021.
[89] Gaffney-Stomberg E, Nakayama AT, Guerriere KI, Lutz LJ, Walker LA, Staab JS, et al. Calcium and vitamin D supplementation and bone health in Marine recruits: Effect of season. Bone. 2019 Jun;123:224-233. doi: 10.1016/j.bone.2019.03.021.
[90] Gaffney-Stomberg E, Lutz LJ, Rood JC, Cable SJ, Pasiakos SM, Young AJ, et al. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. Bone. 2014 Nov;68:46-56. doi: 10.1016/j.bone.2014.08.002.
[91] Gaffney-Stomberg E, Lutz LJ, Rood JC, Cable SJ, Pasiakos SM, Young AJ, et al. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. Bone. 2014 Nov;68:46-56. doi: 10.1016/j.bone.2014.08.002.
[92] Silk LN, Greene DA, Baker MK, Jander CB. The effect of calcium and vitamin D supplementation on bone health of male Jockeys. J Sci Med Sport. 2017 Mar;20(3):225-229. doi: 10.1016/j.jsams.2016.08.004.
[93] O'Connor E, Mølgaard C, Michaelsen KF, Jakobsen J, Lamberg-Allardt CJ, Cashman KD. Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls. Br J Nutr. 2007 Apr;97(4):661-6. doi: 10.1017/S0007114507433050.
[94] Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42. PMID: 20199985.
[95] Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015 Sep;102(3):695-703. doi: 10.3945/ajcn.114.093906.
[96] Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015 Sep;102(3):695-703. doi: 10.3945/ajcn.114.093906.
[97] Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015 Sep;102(3):695-703. doi: 10.3945/ajcn.114.093906.
[98] García-Martín A, Quesada Charneco M, Alvárez Guisado A, Jiménez Moleón JJ, Fonollá Joya J, Muñoz-Torres M. Effect of milk product with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women: randomized trial. Med Clin (Barc). 2012 Feb 4;138(2):47-51. doi: 10.1016/j.medcli.2011.04.033.
[99] Shedd-Wise KM, Alekel DL, Hofmann H, Hanson KB, Schiferl DJ, Hanson LN, et al. The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women. J Clin Densitom. 2011 Jan-Mar;14(1):47-57. doi: 10.1016/j.jocd.2010.11.003.
[100] Shedd-Wise KM, Alekel DL, Hofmann H, Hanson KB, Schiferl DJ, Hanson LN, et al. The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women. J Clin Densitom. 2011 Jan-Mar;14(1):47-57. doi: 10.1016/j.jocd.2010.11.003.
[101] Haya-Palazuelos J, Castelo-Branco C, Cancelo-Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, et al. Safety and efficacy of ossein-hydroxyapatite complex for the prevention of osteoporosis during perimenopause. A three year follow-up study. Maturitas. 2015 May 1;81(1):170. doi: 10.1016/j.maturitas.2015.02.206.
[102] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[103] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[104] Haya-Palazuelos J, Castelo-Branco C, Cancelo-Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, et al. Safety and efficacy of ossein-hydroxyapatite complex for the prevention of osteoporosis during perimenopause. A three year follow-up study. Maturitas. 2015 May 1;81(1):170. doi: 10.1016/j.maturitas.2015.02.206.
[105] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[106] Castelo-Branco C, Cancelo Hidalgo MJ, Palacios S, Ciria-Recasens M, Fernández-Pareja A, Carbonell-Abella C, et al. Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. Climacteric. 2020 Jun;23(3):252-258. doi: 10.1080/13697137.2019.1685488.
[107] Fernández-Pareja A, Hernández-Blanco E, Pérez-Maceda JM, Riera Rubio VJ, Palazuelos JH, Dalmau JM. Prevention of osteoporosis: four-year follow-up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite compound. Clin Drug Investig. 2007;27(4):227-32. doi: 10.2165/00044011-200727040-00001.
[108] Fernández-Pareja A, Hernández-Blanco E, Pérez-Maceda JM, Riera Rubio VJ, Palazuelos JH, Dalmau JM. Prevention of osteoporosis: four-year follow-up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite compound. Clin Drug Investig. 2007;27(4):227-32. doi: 10.2165/00044011-200727040-00001.
[109] The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age [Internet]. Melbourne, VIC: RACGP; c2016.; 2017 [cited 2020 Jun 9]. Available from: https://www.racgp.org.au/getattachment/2261965f-112a-47e3-b7f9-cecb9dc4fe9f/Osteoporosis-prevention-diagnosis-and-management-in-postmenopausal-women-and-men-over-50-years-of-age.aspx.
[110] Ciria-Recasens M, Blanch-Rubió J, Coll-Batet M, Del Pilar Lisbona-Pérez M, Díez-Perez A, Carbonell-Abelló J, et al. Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study. Clin Drug Investig. 2011 Dec 1;31(12):817-24. doi: 10.1007/BF03256920.
[111] Ciria-Recasens M, Blanch-Rubió J, Coll-Batet M, Del Pilar Lisbona-Pérez M, Díez-Perez A, Carbonell-Abelló J, et al. Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study. Clin Drug Investig. 2011 Dec 1;31(12):817-24. doi: 10.1007/BF03256920.
[112] Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ, Palacios S, Haya-Palazuelos J, Carbonell-Abelló J, et al. Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis. Menopause. 2009 Sep-Oct;16(5):984-91. doi: 10.1097/gme.0b013e3181a1824e.
[113] Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ, Palacios S, Haya-Palazuelos J, Carbonell-Abelló J, et al. Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis. Menopause. 2009 Sep-Oct;16(5):984-91. doi: 10.1097/gme.0b013e3181a1824e.
[114] Pelayo I, Haya J, De la Cruz JJ, Seco C, Bugella JI, Diaz JL, et al. Raloxifene plus ossein-hydroxyapatite compound versus raloxifene plus calcium carbonate to control bone loss in postmenopausal women: a randomized trial. Menopause. 2008 Nov-Dec;15(6):1132-8. doi: 10.1097/gme.0b013e318170af33.
[115] Pines A, Raafat H, Lynn AH, Whittington J. Clinical trial of microcrystalline hydroxyapatite compound ('Ossopan') in the prevention of osteoporosis due to corticosteroid therapy. Curr Med Res Opin. 1984;8(10):734-42. doi: 10.1185/03007998409110124.
[116] Pines A, Raafat H, Lynn AH, Whittington J. Clinical trial of microcrystalline hydroxyapatite compound ('Ossopan') in the prevention of osteoporosis due to corticosteroid therapy. Curr Med Res Opin. 1984;8(10):734-42. doi: 10.1185/03007998409110124.
[117] Stellon A, Davies A, Webb A, Williams R. Microcrystalline hydroxyapatite compound in prevention of bone loss in corticosteroid-treated patients with chronic active hepatitis. Postgrad Med J. 1985 Sep;61(719):791-6. doi: 10.1136/pgmj.61.719.791.
[118] Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257-64.
[119] Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011 Aug;25(4):585-9.
[120] Jahnke GD, Choksi NY, Moore JA, Shelby MD. Thyroid toxicants: assessing reproductive health effects. Environ Health Perspect. 2004 Mar;112(3):363-8.
[121] Pałkowska-Goździk E, Lachowicz K, Rosołowska-Huszcz D. Effects of dietary protein on thyroid axis activity. Nutrients. 2018;10(1):5. doi:10.3390/nu10010005.
[122] Messina M. Soy and health update: Evaluation of the clinical and epidemiologic literature. Nutrients. 2016 Nov;8(12):1-42.
[123] Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: A review of the relevant literature. Thyroid. 2006 Mar;16(3):249-58.
[124] EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Risk assessment for peri‐and post‐menopausal women taking food supplements containing isolated isoflavones. EFSA Journal. 2015 Oct;13(10):4246.
[125] Rizzo G, Baroni L. Soy, soy foods and their role in vegetarian diets. Nutrients. 2018 Jan 5;10(1):43. doi:10.3390/nu10010043.
[126] Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: A review of the relevant literature. Thyroid. 2006 Mar;16(3):249-58.
[127] Lu LJ, et al. Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res. 2000 Mar 1;60(5):1299-305.
[128] Kucuk O. Soy foods, isoflavones, and breast cancer. Cancer. 2017 Jun 1;123(11):1901-1903. doi: 10.1002/cncr.30614.
[129] Zaheer K, Humayoun AM. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr. 2017 Apr 13;57(6):1280-1293. doi: 10.1080/10408398.2014.989958.
[130] Messina M. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients. 2016 Nov;8(12):1-42.
[131] Rizzo G, Baroni L. Soy, soy foods and their role in vegetarian diets. Nutrients. 2018 Jan 5;10(1):43. doi:10.3390/nu10010043.
[132] Guha N, Kwan ML, Quesenberry CP Jr, Weltzien EK, Castillo AL, Caan BJ. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2009 Nov;118(2):395-405. doi: 10.1007/s10549-009-0321-5. Epub 2009 Feb 17. PubMed PMID: 19221874
