Inhibition of markers of bone resorption by consumption of vitamin D and calcium-fortified soft plain cheese by institutionalised elderly women

Acceleration of bone remodelling increases the risk of fragility fractures. The objective of the present study was to explore in elderly women whether a vitamin D and Ca-fortified dairy product providing about 17–25 % of the recommended intakes in vitamin D, Ca and proteins would reduce secondary hyperparathyroidism and bone remodelling in a way that may attenuate age-related bone loss in the long term. Thirty-seven institutionalised women, aged 84·8 (sd 8·1) years, with low serum 25-hydroxyvitamin D (5·5 (sd 1·7) ng/ml) were enrolled into a multicentre open trial to consume during 1 month two servings of soft plain cheese made of semi-skimmed milk providing daily 686 kJ (164 kcal), 2·5 μg vitamin D, 302 mg Ca and 14·2 g proteins. The primary endpoint was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX), selected as a marker of bone resorption. Thirty-five subjects remained compliant. Mean serum changes were: 25-hydroyvitamin D, +14·5 % (P = 0·0051); parathyroid hormone (PTH), − 12·3 % (P = 0·0011); CTX, − 7·5 % (P = 0·01); tartrate-resistant acid phosphatase isoform 5b (TRAP 5b), − 9·9 % (P < 0·0001); albumin, +6·2 % (P < 0·0001); insulin-like growth factor-I (IGF-I),+16·9 % (P < 0·0001); osteocalcin, +8·3 % (P = 0·0166); amino-terminal propeptide of type 1 procollagen (P1NP),+19·3 % (P = 0·0031). The present open trial suggests that fortified soft plain cheese consumed by elderly women with vitamin D insufficiency can reduce bone resorption markers by positively influencing Ca and protein economy, as expressed by decreased PTH and increased IGF-I, respectively. The rise in the bone formation marker P1NP could be explained by a protein-mediated increase in IGF-I. Thus, such a dietary intervention might uncouple, at least transiently, bone resorption from bone formation and thereby attenuate age-related bone loss.

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Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Acta Endocrinologica ◽

10.1530/eje-11-0132 ◽

2011 ◽

Vol 165 (1) ◽

pp. 1-10 ◽

Cited By ~ 115

Author(s):

Pierre J Marie ◽

Moustapha Kassem

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Bone Matrix ◽

Bone Fragility ◽

Osteoblastic Cell ◽

Medline Search ◽

Cell Functions ◽

Age Related ◽

Increased Risk

ObjectiveAge-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration.MethodsA limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010.Results and discussionWe present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.

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Effect of low-dose of recombinant human growth hormone on bone metabolism in elderly women with osteoporosis

Acta Endocrinologica ◽

10.1530/eje.0.1470339 ◽

2002 ◽

pp. 339-348 ◽

Cited By ~ 22

Author(s):

T Sugimoto ◽

H Kaji ◽

D Nakaoka ◽

M Yamauchi ◽

S Yano ◽

...

Keyword(s):

Growth Hormone ◽

Lumbar Spine ◽

Side Effects ◽

Bone Resorption ◽

Bone Formation ◽

Low Dose ◽

Elderly Women ◽

Serum Concentrations ◽

Gh Treatment ◽

Igf I

BACKGROUND: There has been increasing evidence that the growth hormone (GH)-IGF-I axis plays an important part in the maintenance of bone mass. However, controversy still exists as to the effect of GH treatment on bone mineral density (BMD) in elderly patients with osteoporosis. OBJECTIVE: To investigate the effect of low-dose GH treatment on markers of body composition and bone turnover, serum concentrations of IGF-I and IGF-binding proteins (IGFBPs), and BMD at the radius and lumbar spine in eight elderly Japanese women with osteoporosis. METHODS: Participants were treated with GH as a single daily subcutaneous injection (0.125 IU/kg per week; 0.00595 mg/kg per day) for 48 weeks. RESULTS: Markers of bone formation and bone resorption were both increased up to 24 weeks of GH treatment. The bone formation markers remained increased during GH treatment, whereas the bone resorption markers returned to baseline values after 24 weeks of GH treatment. GH treatment caused a rapid (within 2 weeks) and sustained increase in serum IGF-I concentration. As for IGFBPs, serum concentrations of IGFBPs-2, -3 and -4 did not change significantly during GH treatment. In contrast, GH treatment caused a gradual increase in serum IGFBP-5 concentration, with a significant increase seen 48 weeks after the start of GH treatment. Radial BMD seemed to be increased during the late period of GH treatment, although the change was not significant. Lumbar BMD did not change during GH treatment. GH treatment caused a significant increase in hand grip strength. None of the GH-treated participants had new fractures and side effects such as edema and joint pain. Radial BMD was significantly increased after discontinuation of GH treatment for another 48 weeks and a similar tendency was observed at the lumbar spine (7.1+/-2.3% above pretreatment values for the radius and 3.6+/-2.0% for the lumbar spine). CONCLUSIONS: Low-dose GH treatment attenuated the decrease in muscle strength and bone mass in elderly women without side effects, although changes in nutrition and exercise might affect BMD. The present findings provide useful information regarding the use of low-dose GH treatment in elderly women with osteoporosis.

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Bone loss in inflammatory disorders

Journal of Endocrinology ◽

10.1677/joe-08-0568 ◽

2009 ◽

Vol 201 (3) ◽

pp. 309-320 ◽

Cited By ~ 185

Author(s):

R Hardy ◽

M S Cooper

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Inflammatory Disease ◽

Bone Remodelling ◽

Inflammatory Diseases ◽

Direct Effects ◽

Increase Bone Resorption ◽

Chronic Inflammatory Diseases ◽

Poor Nutrition

Chronic inflammatory diseases of almost any cause are associated with bone loss. Bone loss is due to direct effects of inflammation, poor nutrition, reduced lean body mass, immobility and the effects of treatments, especially glucocorticoids. These mechanisms are complex and interrelated but are ultimately mediated through effects on the bone remodelling cycle. Inflammatory disease can increase bone resorption, decrease bone formation but most commonly impacts on both of these processes resulting in an uncoupling of bone formation from resorption in favour of excess resorption. This review will illustrate these interactions between inflammation and bone metabolism and discuss how these are, and might be, manipulated as therapies for inflammation related bone loss.

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The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid

Lupus ◽

10.1177/09612033211000126 ◽

2021 ◽

Vol 30 (6) ◽

pp. 965-971

Author(s):

Wang Tianle ◽

Zhang Yingying ◽

Hong Baojian ◽

Gu Juanfang ◽

Wang Hongzhi ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Turnover ◽

Bone Metabolism ◽

Bone Turnover Markers ◽

Control Group ◽

Bone Resorption Marker ◽

Amino Terminal ◽

Normal People ◽

Turnover Markers

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

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An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient Rats

Journal of Bone and Mineral Research ◽

10.1359/jbmr.2005.20.6.1065 ◽

2005 ◽

Vol 20 (6) ◽

pp. 1065-1074 ◽

Cited By ~ 10

Author(s):

Pierre J. Marie ◽

Monique Hott ◽

Dominique Modrowski ◽

Cinderella de Pollak ◽

Joel Guillemain ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation

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Novel Osteogenic Factors derived from Functional Food: Role in Prevention of Osteoporosis

Journal of Bone Biology and Osteoporosis ◽

10.18314/jbo.v1i1.9 ◽

2015 ◽

Vol 1 (1) ◽

Author(s):

Masayoshi Yamaguchi

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Functional Food ◽

Human Subjects ◽

Osteoclastic Bone Resorption ◽

Bone Homeostasis ◽

Osteoblastic Bone Formation ◽

Prevention Of Osteoporosis ◽

Osteogenic Effect

<p>Bone homeostasis is maintained through a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss is caused by decreasing in osteoblastic bone formation and increase in osteoclastic bone resorption, thereby leading to osteoporosis. Functional food factors may play a role in<br />the prevention of osteoporosis. Functional food factors including genistein, menaquinone-7 (vitamin K2) and β-cryptoxanthine have been shown to possess a potential osteogenic effect. These factors have been shown to reveal stimulatory effects on osteoblastic bone formation and suppressive effects on osteoclastic<br />bone resorption. Dietary intake of these factors has been shown to reveal preventive effects on bone loss in animal models of osteoporosis and human subjects. This review will introduce our findings concerning roles of functional food factors in regulation of bone homeostasis and prevention of osteoporosis.</p>

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Effect of Cholecalciferol Supplementation on Bone Turnover Markers in Children and Adolescents With Type 1 Diabetes Mellitus

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.556 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A274-A274

Author(s):

Volodymyr I Pankiv ◽

Ivan V Pankiv

Keyword(s):

Diabetes Mellitus ◽

Vitamin D ◽

Bone Formation ◽

Children And Adolescents ◽

Bone Markers ◽

Vitamin D Supplementation ◽

Procollagen Type ◽

Amino Terminal ◽

Cholecalciferol Supplementation

Abstract Background: Cholecalciferol is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Aim of the study: to evaluate the correlation between serum 25(OH)D and bone markers and impact of vitamin D supplementation on serum bone formation [procollagen type 1 amino-terminal propeptide (P1NP)] and bone resorption [β-cross laps (CTx)] markers among children and adolescents with type 1 diabetes mellitus (DM). Materials and Methods: Total 58 children and adolescents with type 1 DM, who were given 2000 UI of cholecalciferol supplementation, were included in the study. These 58 children with available anthropometry, serum biochemistry, 25-hydroxyvitamin D ([25(OH)D]), and parathormone (PTH) were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (β-cross laps [CTx]) markers. Results: The mean age and body mass index of these children were 11.6 ± 2.3 years (boys: 11.7 ± 2.4; girls: 12.2 ± 1.4 years; p = 0.04) and 18.2 ± 3.9 kg/m2 (boys: 18.1 ± 3.8; girls: 17.8 ± 3.4 kg/m2; p = 0.206), respectively. Baseline serum P1NP levels were positively correlated with serum phosphates (r = 0.281, p < 0.001), PTH (r = 0.291, p < 0.001), and CTx (r = 0.425, p < 0.001) but not with age (r = -0.016, p = 0.404), BMI (r = -0.080, p = 0.032), serum calcium (r = -0.038, p = 0.107), and baseline 25(OH)D (r = -0.069, p = 0.035). Postsupplementation serum P1NP and CTx levels maintained similar correlations. There was a significant decline in serum P1NP (from 681 ± 223 ng/ml to 630 ± 279 ng/ml, p < 0.01) and CTx (from 1.63 ± 0.51 ng/ml to 1.37 ± 0.53 ng/ml, p < 0.01) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all supplementation patients, the effect was more marked in serum CTx than P1NP levels. Conclusions: Vitamin D supplementation in children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.

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Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels

Endocrinology ◽

10.1210/en.2015-1855 ◽

2016 ◽

Vol 157 (7) ◽

pp. 2621-2635 ◽

Cited By ~ 23

Author(s):

Seong Hee Ahn ◽

Sook-Young Park ◽

Ji-Eun Baek ◽

Su-Youn Lee ◽

Wook-Young Baek ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

High Fat Diet ◽

Wild Type ◽

High Fat ◽

Free Fatty Acid Receptor

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4−/−) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4−/− and fat-1Tg+ mice over two generations to generate four genotypes of mice littermates: Ffar4+/+;fat-1Tg−, Ffar4+/+;fat-1Tg+, Ffar4−/−;fat-1Tg−, and Ffar4−/−;fat-1Tg+. Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1Tg+ mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In a high-fat diet-fed model, male fat-1Tg+ mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

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The Paradoxical Role of Uric Acid in Osteoporosis

Nutrients ◽

10.3390/nu11092111 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2111 ◽

Cited By ~ 2

Author(s):

Kun-Mo Lin ◽

Chien-Lin Lu ◽

Kuo-Chin Hung ◽

Pei-Chen Wu ◽

Chi-Feng Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Uric Acid ◽

Bone Resorption ◽

Bone Formation ◽

Inflammatory Cytokines ◽

Bone Fracture ◽

Health Concern ◽

Free Oxygen Radicals ◽

Increase Bone Resorption

Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.

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Bone changes due to pregnancy and lactation: influence of vitamin D status

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.4.e400 ◽

1986 ◽

Vol 251 (4) ◽

pp. E400-E406 ◽

Cited By ~ 4

Author(s):

P. J. Marie ◽

L. Cancela ◽

N. Le Boulch ◽

L. Miravet

Keyword(s):

Vitamin D ◽

Bone Resorption ◽

Bone Formation ◽

Trabecular Bone ◽

Formation Rate ◽

Vitamin D Status ◽

Bone Formation Rate ◽

Bone Calcium ◽

Pregnancy And Lactation ◽

Stimulation Of

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.

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