Open-label Study to Evaluate the Effect of MBP-80 on Bone Remodelling

A 12-week, Open-label Study to Evaluate the Effect of MBP-80 (200g of Yogurt With Fortified Calcium Content and MBP 80 mg) on Bone Remodelling as Assessed by Bone Turnover Markers in Early Postmenopausal Women

This study will determine if daily oral intake of 200g of a marketed yogurt with fortified calcium content and a milk basic protein (MBP)80 mg benefits on bone cells activity in postmenopausal women. The efficacy of the product is measured by examining the variation of biochemical markers of bone turnover. MBP 80 is a particular protein contained in milk; it has been added to the yogurt provided for this study. The effects of MBP 80 on the quality of bone tissue have not yet been proven.

The morbidity and mortality associated with osteoporotic related fractures is devastating in terms of disability to an individual and cost to the global economy. As the world's population ages, this will present a major public health issue since a larger proportion of women remain undiagnosed and untreated even with the availability of therapies and calcium and vitamin D supplements. Consequently, it remains important to evaluate dairy products (milk, cheese, and yogurt) that can be safely provided as a supplement for bone health in addition to the current pharmacological treatments.

The rationale of this study is to assess the beneficial effect of a daily dietary supplement of MBP 80 mg in a yogurt matrix with fortified calcium content on bone remodelling in healthy early postmenopausal women with neither osteoporosis nor estrogens/progestin therapy.

Inclusion Criteria:

• Early postmenopausal women, aged 45-60 yrs old inclusive, with 1-5 yrs since last menses; naturally or surgically menopausal as a result of bilateral oophorectomy. Hysterectomized (≤ 5 yrs) women 50-60 yrs old.
• Lumbar Spine (L.S.;L1-L4) BMD > 0.772 g/cm2 (T-score of -2.5 on Hologic) and,
• Femoral Neck BMD > 0.572 g/cm2 (T-score of -2.5 on Hologic) and,
• Total Hip BMD > 0.637 g/cm2 (T-score of -2.5 on Hologic).
• Subjects must sign the Ethic Committee approved Informed Consent Form before any study procedure is initiated.

Exclusion Criteria:

• Any intake of calcium and vitamin D supplements including multivitamins, nutritional or dietary supplements of any kind containing calcium and vit D within 3 months prior to screening visit 1A.
• Daily dietary calcium intake > 600 mg as assessed by the Calcium Intake Calculator (Appendix E).
• Subjects who already suffer from osteoporosis on the basis of a low BMD T-score ≤ - 2.5 at any site or a personal history of fragility fracture after age 40.
• Any past or present use of:
• Bisphosphonate
• PTH or PTH derivatives, eg. teriparatide
• Androgens, anabolic steroids or testosterone
• Tibolone
• Calcitriol
• Strontium ranelate
• Lithium, chronic warfarin or heparin use > 3 months, anticonvulsants (benzodiazepines are allowed), gonadotrophin-releasing hormone agonists, glitazones.
• Administration of any of the following treatments within the last 3 months prior to screening:
• Glucocorticosteroids (> 5 mg prednisone equivalent per day for > 10 days)
• Systemic hormone replacement therapy
• Selective estrogen receptor modulators (SERMs), eg, raloxifene
• Calcitonin
• Any unapproved hormone-like treatment in the opinion of the Principal Investigator (P.I.), i.e. phytoestrogens, isoflavones, etc.
• Antacids, H2 blockers, proton pump inhibitors for > 10 days
• Iron supplements for > 10 days
• Any condition or disease that may, according to the P.I., interfere with the evaluation of L.S. and Hip BMD; including but not limited to: advanced scoliosis or extensive lumbar fusion, less than 2 lumbar vertebrae (L1-L4) evaluable for DXA.
• Hyper or hypothyroidism: patients on stable dose of thyroid treatment with normal TSH will be allowed. Lab values for TSH must be normal or slightly abnormal, though clinically non significant in the opinion of the P.I.
• Current hyper or hypoparathyroidism, in the opinion of the P.I.
• Current hypocalcemia, in the opinion of the P.I.
• Vit D insufficiency (25-OH vitamin D level < 40 nmol/L)
• Significantly impaired renal function hereby defined as an estimated GFR ≤ 60 mL/min/ 1.73 m2 (4-variable MDRD equation).
• Rheumatoid arthritis.
• Paget's disease of bone.
• Any history of cancer within the past 5 years (except for basal cell carcinoma, dermal squamous cell carcinoma with 6 month remission and cervix carcinoma in situ).
• Any bone disease, i.e. osteomalacia or osteogenesis imperfecta.
• Chronic asthma, in the opinion of the P.I.
• Malabsorption syndrome (coeliac disease, inflammatory bowel disease, gastric bypass).
• Height, weight and girth which may preclude accurate DXA measurement; BMI outside ranges between 18.5 and 35 inclusive.
• Variation of more than 2 kg (gain or loss) within 2 months of the Screening.
• Presence of any vertebral fracture on the screening VFA (Vertebral Fracture Assessment) measured by DXA.
• Any previous or ongoing clinically significant illness that, in the opinion of the P.I., could prevent the patient from completing the study.
• Evidence of alcohol or substance abuse within the last 12 months that the P.I. believes would interfere with understanding or completing the study.
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).