Interactive effects of milk basic protein supplements and habitual physical activity on bone health in older women: A 1-year randomized controlled trial.
International Dairy Journal, 2010; 20(10), pp. 724–730
Aoyagia Y, Parka H, Parka S, Yoshiuchib K, Kikuchib H, Kawakamic H, Moritac Y, Onoc A, Shephardd R.J.
A 1-year randomized controlled trial examined effects of milk basic protein (MBP) supplementation (40 mg day−1) and daily physical activity (step count and duration of exercise > 3 metabolic equivalents [METs]) on bone metabolism, forearm bone mineral density (BMD) and a calcaneal osteosonic index (OSI) in 79 females aged 65–86 years. MBP did not affect osteocalcin or bone-specific alkaline phosphatase, but at 12 months, excretion of deoxypyridinoline and cross-linked N-teleopeptides of type I collagen (NTx) were significantly less than in controls. Experimental subjects also maintained BMD and had a 1.5% increase of OSI at 12 months. After adjustments for age and baseline bone parameters, osteocalcin, deoxypyridinoline, NTx and/or OSI at 12 months were significantly related to step count and/or duration of activity > 3 METs. MBP reduced markers of bone loss, particularly in the lower extremities. Reduced resorption of bone was also associated with moderate-intensity/duration exercise, MBP therapy interacting significantly with habitual physical activity.
Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women.
Osteoporos Int. 2007 Mar;18(3):385-90.
Uenishi K, Ishida H, Toba Y, Aoe S, Itabashi A, Takada Y.
Effect of milk basic protein on bone metabolism in healthy young women.
INTRODUCTION: Milk has more beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The object of this study was to examine the effect of MBP on the bone mineral density and bone metabolism of healthy young women.
METHODS: Thirty-five healthy young women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for 6 months. The bone mineral density (BMD) of the lumbar vertebrae L2-L4 of each subject was measured by dual-energy X-ray absorptiometry (DXA) at 0 and 6 months of treatment. Serum and urine indexes of bone metabolism were measured at 0, 3 and 6 months. All subjects completed the study in accordance with the protocol.
RESULTS: The mean rate of gain of lumbar BMD in the MBP group (1.57%) was significantly higher than in the placebo group (0.13%, P=0.042). When compared with the placebo group, urinary cross-linked N-telopeptides of type-I collagen (NTx) were significantly decreased, and serum osteocalcin was significantly increased in the MBP group at 6 months.
CONCLUSION: These results suggested that MBP supplementation was effective in increasing BMD in young women and that this increase in BMD may be primarily mediated through the promotion of bone formation and inhibition of bone resorption by MBP supplementation.
Milk basic protein increases alveolar bone formation in rat experimental periodontitis.
J Periodontal Res. 2007 Feb;42(1):85-9.
Seto H, Toba Y, Takada Y, Kawakami H, Ohba H, Hama H, Horibe M, Nagata T.
BACKGROUND AND OBJECTIVE: It is conceivable that the active components extracted from milk whey protein (i.e. milk basic protein, MBP) stimulate bone formation and suppress bone resorption. Periodontitis is characterized by excessive alveolar bone resorption. We examined whether milk basic protein could recover alveolar bone loss in rat experimental periodontitis.
MATERIAL AND METHODS: A nylon ligature was placed around the cervix of molars in 8-wk-old male Fischer rats for 20 d. Then, the ligature was removed and a powder diet containing 0.2 or 1.0% milk basic protein was provided daily for another 45-90 d. On days 45 and 90, the maxillae were extracted and analyzed using microcomputerized tomography (micro-CT), followed by histological analysis.
RESULTS: Micro-CT images showed that alveolar bone resorption was severely induced around the molar by the 20-d ligature procedure. Treatment with high-dose milk basic protein (1.0%) clearly recovered ligature-induced alveolar bone resorption on days 45 and 90, whereas low-dose milk basic protein (0.2%) did not show such a clear effect. Histological examination clarified that the osteoid thickness of alveolar bone was dose dependently increased by milk basic protein treatment for 90 d.
CONCLUSION: These findings suggest that a systemic administration of milk basic protein may be effective for the recovery of alveolar bone loss in periodontitis.
The usefulness of strontium as an adjuvant to calcium in the remineralization of the skeleton in man.
Bull Hosp Joint Dis. 1952 Apr; 13(1): 59-66.
Shorr E, Carter AC.
The results are described of a current investigation of the possible value of Sr as an adjuvant to Ca in the remineralization of the depleted skeleton in a variety of derangements of bone metabolism in man. Sr, in amounts sufficient to achieve significant retention of this element, has been well tolerated over several years of administration and without toxic effects. The retention of Sr is augmented by agents such as Vitamin D, estrogens, and androgens in a similar manner to Ca. When given in equal amounts, Sr is found to have certain distinct advantages over Ca for the remineralization of the skeleton. There is greater retention of Sr; and when the ceiling for Ca retention has been reached, the addition of Sr results in a retention of the latter. Hence, the deposition of Ca plus Sr is greater than the total Ca storage which can be achieved with Ca alone, regardless of Ca intake and auxiliary therapy. This combination should hasten the rate of remineralization of the skeleton as compared with Ca alone, an inference that is supported by the objective and subjective improvement observed under the combined regime. Maximal retention of Sr and Ca is achieved with the assistance of three auxiliary agents-Vitamin D, estrogens and androgens. Finally, the usefulness of Sr as a means of measuring mineral salt turnover in bone is suggested.
The effect of strontium lactate in the treatment of osteoporosis.
Proc Staff Meetings Mayo Clin. 1959; 34(13): 329-34.
McCaslin FE Jr, Janes JM.
A study has been made of the case records of 32 patients treated for osteoporosis with strontium lactate, or strontium lactate with hormones, and then traced for various periods with repeated physical and roentgenographic examinations. Marked subjective improvement was experienced by 84 percent of the patients. Although the mechanism of action of strontium lactate in the treatment of osteoporosis remains to be elucidated, the therapeutic value of the drug appears to be established.
Histomorphometry of Bone Changes in Stable Strontium Therapy.
Trace Subst Env Health. 1985; 19: 193-208.
Marie PJ, Skoryna SC, Pivon RJ Chabot G, Glorieux FH, Stara JF
Previous studies in rats have shown that low dosage of stable Sr2 added to drinking water stimulates bone formation (7). Low doses of Sr2 are currently used in treating metastic bone cancer and osteoporosis (17). In the present paper, histomorphometric changes in transiliac bone biopsy material obtained in six patients, before and after 6 months of Stable Strontium Therapy (SST), are reported. All cases had clinically diagnosable osteoporosis. Sr2 was administered as Sr carbonate, 600-700mg per day. No side effects were observed. Serum Sr:Ca ratio changed from pre SST of 1:1250 (±176) to 1:12 (±0.35) post SST. Bone Sr:Ca ratio changed from 1:1276 (±852) to 1:166 (±74). Mean bone Ca2 increased slightly but not significantly. Following SST, all histological parameters of bone formation increased, while bone resorption remained unchanged. An increased amount of osteoid tissue was observed, associated with stimulation of bone formation at the tissue level. No significant elevation of trabecular bone volume was found. Clinical observations suggest that the response to SST is better in younger (post-menopausal) cases than in senile osteoporosis. Long-term studies are necessary to determine whether the increase in trabecular calcified bone volume observed in rodents, following low dosage of Sr2 , also occurs in human subjects.
Strontium ranelate reduces the risk of hip fractures in women with postmenopausal osteoporosis.
Osteoporos Int. 2002 Nov;13 (Suppl 3): S14(AbsO14).
Reginster J-Y, Sawicki A, Devogelaer JP, Padrin JM, Kaufma JM, Doyle DV, Fardellone P, Graham J, Felsenberg D, Tulassay Z, Soren-Sen OH, Luisett G, Rizzoli R, Blotman F, Pheneko C, Meunier PJ.
Preclinical and clinical studies have demonstrated that strontium ranelate (S12911) is a bone forming agent with anti-resorptive activity which increases bone mass and bone biomechanical resistance. A dose-ranging clinical study (STRATOS) has determined the 2g-daily dose to be the optimal dose in increasing lumbar BMD.
A randomised double-blind, placebo controlled, phase 3 clinical trial (SOTI study), involving 72 centres in 12 countries, was designed to assess the anti-vertebral fracture efficacy and safety of S12911 (2g/d orally) in women with postmenopausal osteoporosis over a 3 year period. Patients also received daily calcium and vitamin D supplements. The patients (n = 1649) were included in two parallel groups [age: 69.7 (7.3); Lumbar BMD: 0.73 (0.12); mean (SD)], 87.5% of them having at least one prevalent vertebral fracture (2.2 prevalent VF per patient). A 41% reduction in relative risk (RR) of experiencing a first new vertebral fracture (semi-quantitative assessment) was observed with strontium ranelate throughout the 3 year study compared to placebo, 139 patients with VF versus 222 respectively (RR = 0.59, 95%CI [0.48;0.73], p We infer that strontium ranelate is a new orally effective and safe treatment of vertebral osteoporosis with a unique mechanism of action. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.
The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.
N Engl J Med. 2004 Jan 29;350(5):459-68.
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY.
BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density.
METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months.
RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
Mechanisms of action and therapeutic potential of strontium in bone.
Calcif Tissue Int 2001 Sep; 69(3): 121-9.
Marie PJ, Ammann P, Boivin G, Rey C.
The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.
Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial.
Osteoporos Int 2002 Dec; 13(12): 925-31.
Reginster JY, Deroisy R, Dougados M, Jupsin I, Colette J, Roux C.
Early postmenopausal women ( n = 160) were randomised to receive placebo or strontium ranelate (SR) 125 mg/day, 500 mg/day or 1 g/day for 2 years (40 participants per group). All participants received calcium 500 mg/day. The primary efficacy parameter was the percent variation in lumbar bone mineral density (BMD), measured using dual-energy X-ray absorptiometry. Secondary efficacy criteria included hip BMD and biochemical markers of bone turnover. At month 24, SR 1 g/day significantly increased lumbar BMD compared with placebo [mean (SD) 5.53% (5.12);