Milk Supplementation and Bone Health in Children

Effects of Yili Child Formula Milk on Bone Health in 4-6 Year Children: a 12-month Randomized Controlled Trial

Objectives: to examine the effects of a Yili child formula milk and regular milk on bone health and growth in young children.

Study design: cluster randomized controlled trial.

Setting: kindergartens in Hui-ning County of Gansu Province, China (north west).

Participants: >=246 apparent healthy children aged 4-6 years old.

Interventions:

(I) Yili child formula milk (QQ star formula, SCI-PRO NUTR5+6TM), 195 ml *2 /day; (II) Yili regular milk (pure milk), 195ml*2 /day; (III) Controls: about 50g/d grain foods (containing 20-30 g carbohydrates), e.g. bread.

Interventional Duration: 12 months.

Outcome measures: determined at 0, 6 and 12 months post treatments. Primary outcomes: bone density and bone mineral contents at the forearm and heel, bone biomarkers.

Secondary outcomes: (1) anthropometric indices: weight, height, waist circumference, etc.; (2) immune status.

Other measures: dietary intakes, physical activities, general information, medical information, adverse of side effects.

Data Analyses: The one-year changes and percent changes in the primary and secondary outcomes will be compared among the 3 groups.

Study Overview

• Status: Enrolling by invitation
• Conditions: Bone Density Increased; Body Height
• Intervention / Treatment: Dietary supplement: Formula milk; Dietary supplement: Regular milk; Other: Control foods

• Study Type: Interventional
• Enrollment (Anticipated): 254
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Gangshu
    • Lanzhou, Gangshu, China, 730000
      • LanZhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 6 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged between 4-6 years;
• female and male
• Can be enrolled into kindergarten/school as a normal child.
• Be willing to drinking milk daily.

Exclusion Criteria:

• Milk allergy or intolerance, did not to be used to drinking milk;
• Had the following diseases/conditions confirmed by a hospital: serious diseases of heart, liver, kidney, brain, hematopoietic system, immunity, thyroid or cancer that need to be hospitalization for more than 1 week or take medication(s) for more than 1 month with the past two years.
• having infectious diseases, e.g., tuberculosis, hepatitis, etc.
• Taking vitamin D, calcium tables or nutrient package;
• Consumed more than 3 times (>600ml) milk each week in the previous month.
• Be not willing to provide informed consent, or have other conditions that were considered to be unsuitable for the study by the investigators.
• Increases of body health were out of the range between 5-8 cm in the last year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Formula Milk; Formula milk designed for young children aged over 3 years; Dosage: 195 ml/time; Frequence: 2 times /day; Duration: 12 months	Dietary supplement: Formula milk; Brand name: Yili (QQ star formula milk); Type: SCI-PRO NUTRI 5+6TM formula milk designed for young children aged over 3 years; Dosage: 195ml*2/d; Intervention duration: 12 months
Active Comparator: Regular milk; Regular milk (pure milk); Dosage: 195 ml/time; Frequence: 2 times /day; Duration: 12 months	Dietary supplement: Regular milk; Brand name: Yili； Type: regular milk (pure milk); Dosage: 195ml*2/d; Intervention duration: 12 months
Other: Control foods; Grain foods: e.g., bread; Dosage: 20-40 g/time; Frequence: 2 times /day; Duration: 12 months	Other: Control foods; Brand: N/A; Food type: grain foods (e.g., bread); Dosage: 20-40g * 2/d grain foods Intervention duration: 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline bone mineral density (BMD) at 12 months	BMD (g/cm2) determined by a dual energy x-ray absorptiometry (DXA) at the left forearm and heel	0 and 12 months
Change from baseline bone mineral density (BMD) at 6 months	BMD (g/cm2) determined by DXA at the left forearm and heel	0 and 6 months
Change from baseline bone mineral contents (BMC) at 12 months	BMC (g) determined by DXA at the left forearm and heel.	0 and 12 months
Change from baseline bone mineral contents (BMC) at 6 months	BMC (g) determined by DXA at the left forearm and heel.	0 and 6 months
Change from baseline of bone-specific alkaline phosphatase at 12 months	Bone turnover marker 1: Bone-specific alkaline phosphatase	0 and 12 months
Change from baseline of bone-specific alkaline phosphatase at 6 months	Bone turnover marker 1: Bone-specific alkaline phosphatase	0 and 6 months
Change from baseline of osteocalcin at 12 months	Bone turnover marker 2: osteocalcin	0 and 12 months
Change from baseline of osteocalcin at 6 months	Bone turnover marker 2: osteocalcin	0 and 6 months
Change from baseline of C-terminal telopeptide of type I collagen at 12 months	Bone turnover marker 3: C-terminal telopeptide of type I collagen	0 and 12 months
Change from baseline of C-terminal telopeptide of type I collagen at 6 months	Bone turnover marker 3: C-terminal telopeptide of type I collagen	0 and 6 months
Change from baseline of tartrate resistant acid phosphatase at 12 months	Bone turnover marker 4: tartrate resistant acid phosphatase	0 and 12 months
Change from baseline of tartrate resistant acid phosphatase at 6 months	Bone turnover marker 4: tartrate resistant acid phosphatase	0 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline body weight at 12 months	Anthropometric indices: body weight	0 and 12 months
Change from baseline body height at 12 months	Anthropometric indices: body height	0 and 12 months
Change from baseline biomarker of body growth at 12 months	Biomarker of body growth: insulin-like growth factor 1	0 and 12 months
Change from baseline immune globulin M (Ig M）at 12 months	Immune status: Blood Ig M	0 and 12 months
Change from baseline immune globulin G (Ig G）at 12 months	Immune status: Blood Ig G	0 and 12 months
Change from baseline immune globulin G (Ig A）at 12 months	Immune status: Blood Ig A	0 and 12 months
Change from baseline whit blood cell at 12 months	Immune status: whit blood cell	0 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of blood total 25-hydroxide-vitamin D (25-OH-VD)	Serum 25-OH-VD	0, 6 and 12 months
Concentrations of blood parathyroid Hormone (PTH)	Serum PTH	0, 6 and 12 months
Nutritional status 1: Body weight	Body weight (in kg)	0, 4, 8 and 12 months
Nutritional status 2: waist circumference	Waist circumference (in cm)	0, 4, 8 and 12 months
Nutritional status 3: middle-arm circumference	Middle-arm circumference (in cm)	0, 4, 8 and 12 months
Nutritional status 4: skinfold thickness	Skinfold thickness (in mm)	0, 4, 8 and 12 months
Total consumption of milk and dairy food	Total consumption of milk and dairy food (in ml/d)	0, 4, 8 and 12 months
Consumption of dietary energy	Consumption of dietary energy (in kcal/d)	0, 4, 8 and 12 months
Consumption of dietary protein	Consumption of dietary protein (in g/d)	0, 4, 8 and 12 months
Consumption of dietary calcium	Consumption of dietary calcium (in mg/d)	0, 4, 8 and 12 months
Number of participants with treatment-related adverse events	Adverse events : assessed by using questionnaires of medical conditions, medications related to milk intake	0, 4, 8 and 12 months
Child behaviors	Child behaviours: assessed by using a Child behavior Questionnaire-- parent version. The minimum and maximum values: 26-78; higher scores mean worse outcome.	0 and 12 months
Physical activity	Physical activity (in MET, h/week): assessed by a Child Physical Activity Questionnaire	0, 4, 8 and 12 months
Concentrations of serum calcium	Serum calcium (mmol/L)	0, 6 and 12 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: LanZhou University
• Investigators: Principal Investigator: Yuming Chen, Ph.D., Sun Yat-sen University; Study Chair: Zhifu Zhao, M. Phil, Inner Mongolia Dairy Technology Research Institute Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Anticipated): October 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: young children; milk; bone health; body growth
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Osteosclerosis
• Other Study ID Numbers: SYSU-51000-20210723-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Published data based on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No