Summary Introduction: Investigations in rodents in addition to in vitro experiments have advised an anabolic affect of particular collagen peptides (SCP) on bone formation and bone mineral density (BMD). The aim of the examine was to analyze the impact of 12-month day by day oral administration of 5 g SCP vs. placebo (CG: management group) on BMD in postmenopausal ladies with major, age-related discount in BMD. Strategies: 131 ladies had been enrolled on this randomized, placebo-controlled double-blinded investigation. The first endpoint was the change in BMD of the femoral neck and the backbone after 12 months. As well as, plasma ranges of bone markers—amino-terminal propeptide of kind I collagen (P1NP) and C-telopeptide of kind I collagen (CTX 1)—had been analysed. Outcomes: A complete of 102 ladies accomplished the examine, however all topics had been included within the intention-to-treat (ITT) evaluation (age 64.3 ± 7.2 years; Physique Mass Index, BMI 23.6 ± 3.6 kg/m2; T-score backbone −2.4 ± 0.6; T-score femoral neck −1.4 ± 0.5). Within the SCP group (n = 66), BMD of the backbone and of the femoral neck elevated considerably in comparison with the management group (n = 65) (T-score backbone: SCP +0.1 ± 0.26; CG −0.03 ± 0.18; ANCOVA p = 0.030; T-score femoral neck: SCP +0.09 ± 0.24; CG −0.01 ± 0.19; ANCOVA p = 0.003). P1NP elevated considerably within the SCP group (p = 0.007), whereas CTX 1 elevated considerably within the management group (p = 0.011). Conclusions: These knowledge reveal that the consumption of SCP elevated BMD in postmenopausal ladies with major, age-related discount of BMD. As well as, SCP supplementation was related to a positive shift in bone markers, indicating elevated bone formation and lowered bone degradation. Key phrases: osteoporosis, collagen hydrolysate, SCP, bone marker, protein supplementation
1. Introduction The etiology of osteoporosis features a lack of bodily exercise, malnutrition, underlying ailments, drug ingestion and non-modifiable elements, comparable to ageing, gender, and acquainted predisposition. Satisfactory prevention or remedy of osteoporosis is a vital aim for particular person and public well being, as a result of osteoporotic bone fractures are chargeable for continual ache, inactivity and invalidity within the aged. It’s estimated that, worldwide, each third ladies, and one in 5 males over the age of fifty, will maintain an osteoporotic-induced bone fracture . At current, there are a variety of therapeutic approaches for the prevention and therapy of osteoporosis. Non-pharmacological approaches, comparable to day by day bodily exercise, smoking cessation and discount of alcohol consumption, are essential cofactors in sustaining bone well being. As well as, supplementation with calcium and vitamin D is advisable in osteoporosis administration, however has not been proven to considerably scale back bone fracture threat. Pharmacological therapy contains substances comparable to bisphosphonates, human monoclonal antibody remedy and selective estrogen receptor modulators. Bisphosphonates are essentially the most widely-used remedy and are designated because the “gold standard” anti-catabolic remedy in fracture prophylaxis. Nevertheless, though the risk-benefit ratio favors therapy with bisphosphonates, some negative effects, comparable to bisphosphonate-related osteonecrosis of the jaw (BRONJ), gastrointestinal problems, ulcer of the mucosa, hypocalcaemia or predisposed renal failure have been described within the literature [2,3,4]. Different remedy varieties concentrate on recombinant synthesized hormones or the manipulation of hormone receptors; nonetheless, these therapies, may additionally induce a variety of negative effects [5,6,7]. In comparison with different continual medicines, compliance issues are comparatively excessive in sufferers taking anti-osteoporotic remedy. Though a relationship with acute or continual negative effects has not been clearly established, about 40% of sufferers with oral bisphosphonates discontinue their remedy through the first 12 months of remedy and roughly 75% of sufferers accomplish that by 5 years . As soon as osteopenia or osteoporosis has been identified, primary therapies, with elevated bodily exercise, a balanced, calcium-rich food regimen and the discount of alcohol and nicotine, could shield in opposition to an additional lack of bone mineral density (BMD). However, these approaches will not be prone to induce an enchancment in BMD. Therefore, efficient and compliant therapeutic approaches presently rank very excessive, significantly in a interval of worldwide demographic change. Preclinical in vitro research or investigations with rodents have proven that administration of collagen peptides elevated the natural part of bones , improved bone metabolism in addition to bone microarchitecture [10,11,12] and enhanced the biomechanical resistance of vertebrae . Furthermore, supplementation with collagen peptides together with calcitonin has proven constructive results in postmenopausal ladies . Within the latter examine, supplementation with collagen peptides led to a statistically vital decreased excretion of bone collagen breakdown merchandise, compared to placebo therapy. Furthermore, the impact of remedy with collagen peptides was persistent over a interval of at the very least three months after the final administration, suggesting an anabolic impact of collagen peptide therapy. Subsequently, within the current examine, the longer-term results of a particular bioactive collagen peptide supplementation on BMD of the decrease backbone and the femoral neck, decided by DXA (twin vitality X-ray absorptiometry), had been examined. For this goal, postmenopausal ladies, aged 46–80 years (imply age 63 years) obtained 5 g particular collagen peptide (SCP)/day or 5 g maltodextrin as a placebo (management group: CG), in a randomized, placebo-controlled design, for 12 months.
2. Topics and Strategies 2.1. Topics and Consort Circulate Diagram A complete of 131 postmenopausal ladies with a lowered bone mineral density (DXA T-score of −1 or decrease on both the femoral neck or the lumbar backbone) had been included on this examine. Particular knowledge relating to affected person recruitment, allocation and follow-up are offered in . Open in a separate window 2.2. Inclusion Standards The inclusion standards had been as follows: feminine topics with lowered BMD of the decrease backbone or the femoral neck, decided by DXA; menopause (amenorrhea for at the very least 1 12 months); no prognosis of any extreme chronical illness or co-morbidity; regular state physique weight and diet; no contraindications for nutraceuticals or protein-rich dietary supplements. 2.3. Exclusion Standards The exclusion standards had been as follows: medical therapy for osteoporosis inside the final 12 months; osteoporosis with excessive threat for bone fractures and indication for medical therapy; allergy to collagen; medical or endocrinological induced osteoporosis; malignant ailments inside the earlier 5 years; diabetes mellitus kind I or II; renal or liver ailments induced by a excessive protein load; current immobilization for a number of weeks. 2.4. Examine Design The investigation was designed as a single-center, potential, randomized, double-blind, placebo-controlled examine. The scientific trial was a section III examine and was carried out based on GCP (good scientific apply) necessities. The examine protocol was accredited by the moral committee of the College of Freiburg. All topics gave written knowledgeable consent. The trial was registered with DRKS-ID: DRKS0009708. The individuals of the examine had been randomly assigned to the therapy group (supplementation with collagen peptides, SCP) or to the placebo group (maltodextrin). Randomization was carried out utilizing a random quantity generator . Blinding of investigators and individuals was not lifted till all knowledge had been entered, the dataset was secured, and the statistical analyses had been carried out. The individuals needed to dissolve the content material of 1 sachet of the investigational product (SCP or maltodextrin) and drink it in a glass of water, earlier than breakfast. Topics in each teams had been instructed by a doctor on the useful results of normal bodily exercise and balanced diet on osteopenia or osteoporosis [16,17]. As well as, topics had been inspired to take calcium and vitamin D dietary supplements in a day by day dose of roughly 0.5–0.8 g (relying on weight) and 400–800 IU, respectively. Nevertheless, the dietary supplements weren’t prescribed, and the consumption was not managed. Compliance, relating to the consumption of the investigational product, was checked by the gathering of unused dietary supplements. As well as, topics had been requested to maintain day by day data about negative effects or different issues associated to the dietary supplements. As well as, blood samples had been taken initially and the tip of the examine for evaluation of bone markers and to judge the protection of the product and to confirm hostile reactions. The examine was carried out over a complete timeframe of 12 months. All phases of the examine are summarized in . Open in a separate window 2.5. DXA BMD of the decrease lumbar backbone (L1–L4) and the femoral neck was measured earlier than and after the 12-month examine interval utilizing DXA (Stratos DR 2D Fan Beam, Degen Medizintechnik, Heppenheim, Germany). 2.6. Dietary Conduct and Bodily Exercise Dietary conduct, with particular reference to macronutrients (fats, carbohydrate, protein), calcium and vitamin D, was evaluated earlier than and on the finish of the examine, through the use of a 4-day dietary protocol. Topics had been requested to fill out the protocol utilizing family measurements on 3 working days and someday off work. The protocols had been analyzed utilizing PRODI 6.0 (Prodi, Stuttgart, Germany). Bodily exercise was assessed with an evaluated questionnaire, in German language, by which the quantity and depth of bodily exercise was queried, and the whole quantity of energy burned by these actions was calculated . 2.7. Protein Supplementation For this examine, a combination of particular bioactive collagen peptides (SCP) with a imply molecular weight of approx. 5 kDa, derived from a fancy multi-step hydrolysis of collagen, was used (FORTIBONE®, GELITA AG, Eberbach, Germany). The sachets containing 5 g SCP or placebo (maltodextrin, CARGILL, Paris, France) had been an identical in look and the merchandise had been equal in taste and texture. 2.8. Pattern Dimension The pattern dimension for the examine was calculated on the premise of the current statistical publication from the Heart of Illness Management (CDC) of March 2012 . An influence evaluation was carried out, primarily based on the idea that the bone mineral density of postmenopausal ladies between 50–59 years was 0.99 ± 0.1 g/cm2, as described by CDC. Contemplating the truth that a remedy with bisphosphonates elevated bone density by about 5%, much like findings by Adam et al. , for SCP a hypothetical development to 1.04 g/cm2 was anticipated. With the usual deviation of 0.1 g/cm2 and an supposed take a look at energy of 80% with a significance degree of α = 0.05 and a calculated drop-out charge of 10%, the variety of 64 individuals per examine group was calculated and regarded adequate. 2.9. Endpoints The first endpoint of this examine was outlined as evaluating variations in bone mineral density (BMD) of the backbone (L1–L4) between each examine teams (SCP versus placebo). The second major end result was outlined as adjustments in BMD of the femoral neck. Adjustments in bone metabolism had been evaluated utilizing the bone biomarkers, amino-terminal propeptide of kind I collagen (P1NP) and C-telopeptide of kind I collagen (CTX 1). Amino-terminal propeptide of kind I collagen (P1NP) was assessed as an indicator of bone formation, whereas C-telopeptide of kind I collagen (CTX 1) was measured as marker for bone resorption. Bone turnover was calculated by evaluating the variety of biomarkers (in ng/mL) within the plasma samples on the finish of the examine (t 12 ), to the worth recorded initially of the examine (t 0 ). An in vitro enzyme immunoassay was used for the quantitative analyses of CTX 1 (BlueGene Biotech., Shanghai, China) and P1NP (Cloud-Clone Corp., Houston, TX, USA). The ELISA exams had been carried out based on the respective instruction manuals. The sensitivities of the exams had been indicated as 12.5 ng/mL and 0.91 ng/mL, respectively. 2.10. Statistical Strategies All quantitative parameters are offered as imply ± SD. Statistical analyses had been carried out utilizing the Statistical Bundle for the Social Sciences Software program (IBM SPSS Statistics 23, IBM, Armonk, NY, USA). The entire statistical analysis was primarily based on the intention-to-treat inhabitants (ITT). Lacking values of all take a look at parameters after the 12-month intervention had been accomplished by a linear development at level (LTAP) examination. Lacking values had been estimated by SPSS, primarily based on the entire examine inhabitants. The baseline values of all parameters had been in contrast between the examine teams, utilizing the unpaired Pupil’s T-test. Testing for adjustments of the first examine aims on bone mineral density between the examine teams was carried out through the use of an Evaluation of the Variances, with the baseline values as Covariate (ANCOVA). Variations between the examination on the baseline degree and after the 12-month intervention inside the examine teams had been carried out by the paired Pupil’s T-test. Alterations within the bone blood biomarkers, P1NP and CTX 1, inside the examine teams, had been examined utilizing the Pupil’s T-test for paired samples. All of the exams within the descriptive evaluation had been carried out as two-sided exams; the degrees of significance had been assessed to α = 0.05 at anybody time. A p-value of < 0.05 was thought-about to point statistical significance. As no hierarchy for the 2 major end-points had been outlined within the protocol, an evaluation, based on Bonferroni–Holm, was carried out.