# Exercise as it relates to Disease/Active Diabetic Kids Beat the Bone Density Blues
## Active Diabetic Kids Beat the Bone Density Blues
### Study Details

This Wiki reviews Physical Activity Increases Bone Mineral Density in Children with Type 1 Diabetes a randomised control trial (RCT) by Dr. Nathalie Farpur-Lambert and colleagues from the Child Health Department, University Hospital, Geneva$^1$. It is published in Medicine and Science in Sports and Exercise, 2012 July 44(7) edition, available from http://www.ncbi.nlm.nih.gov/pubmed/222462171.
This study is high quality, it achieved an 8/10 PEDro ranking for validity and trustworthiness, with bias risk through lack of blinding at fault$^{2,3}$. Further, as an RCT it is the “gold standard” study for assessing intervention, providing Grade II (second highest) evidence$^3$.

### Background

Bone tissue dynamically meets body demands. Density builds and reabsorbs through action of hormones, enzymes and proteins via Osteoblast/Osteoclast cells, in response to exercise stress and calcium deficit respectively$^4$. Childhood/Adolescent bone growth impacts later life bone density$^5$, with Type 1 diabetes (T1DM) children at increased fracture risk from Osteoporosis due to links between diseases, see Table 1$^{16,7}$. Exercise participation for T1DM children may be negatively impacted by requirements to carefully manage blood sugar level to avoid serious hypo/hyperglycaemic events (see Resource 1).
Table 1:Disease Links
| T1DM | Osteoporosis |
| Hypoglycemia | Death/decreased Osteoblast activity Gene expression change: Adipocyte deposition in bone Leptin release-Inhibits bone growth, decreases IGF-1 receptors & chondrocytes$^{9,10}$. |
| Hyperglycaemia | High HbAC1 level overstimulates Osteoclasts$^{10}$. |
| Low Insulin | Decreased Osteoblast formation/activity$^{9.}$ |
The study aimed to analyse weight-bearing physical activity (WBPA) effect on bone mineral mass and to be first to link bone metabolism markers used for adult Osteoporosis research in T1DM children. Blood biomarkers (Table 2) enable early detection of BMD change i.e. 1–2 months post intervention, compared to 1–2 years via DEXA (Dual X-Ray) scan$^{8.}$
Table 2: Biochemical Markers
| Category | Function |
| 25-OH-D | Osteoblast/clast activity |
| Proteins e.g. procollagen-type-1-amino-terminal peptides(PINP), Type-1-collagen-C-Terminal-cross-linking-telopeptides (CTX), Osteocalcin (OC) | Formation/resorbtion of organic skeletal matrix |
| Inorganic skeletal matrix e.g. calcium | Formation of inorganic matrix$^{8-10}$ |

### Research Description

In the 9 month trial, 27 T1DM children and 32 healthy peers were randomly allocated to Intervention; 2 x 90 minutes per week of weight bearing exercise (WBPA) or Control; no exercise or participation in competition sports$^1$. WBPA included skipping, jumping, gymnastics and ball games at maximum Heart Rate 140 bpm$^1$. Exercise was supervised and blood glucose monitored.
Baseline characteristics included:
* Physical activity levels
* Anthropometry
* Bone Mineral Density(BMD) via DEXA scan: Total Body (TB), spine, femur
* Biochemical markers via blood samples (as per Table 2).
* HbA1c levels$^1$.
Measures were repeated post intervention to establish exercise associated change.

### Results

At baseline T1DM children had lower OC, CTX and PINP levels, and higher HbA1c levels$^{1.}$ Mean change was therefore used in analysis.
There was a large effect, mean change for BMD post intervention (>1.4), change for some biomarkers and nil gender difference$^1$. In summary:
BMD
* TB and spine density increased similarly for TIDM and Healthy Intervention$^1$.
* Puberty, increased BMD equally across all groups$^1$.
* Lean Body Mass (LBM) was associated with increased BMD$^{1.}$
Biomarkers
* CTX decreased in Healthy Intervention and Control without statistical significance$^{1.}$
* Low 25-OH-D in Intervention (-7.8) compared to Control (2.6), without BMD association$^1$.
* Nil LBM association with biomarkers$^{1.}$

### Researchers Interpretation

The main finding was regular WBPA improves TB and Lumbar spine BMD accrual in T1DM children as for healthy children$^{1.}$
No interpretation was provided for different baseline measures or 25-OH-D or CXT level change. Discussion of other studies suggested variable CXT levels and resulting bone resorbtion relates to exercise intensity$^1$. This was identified for future research with a larger sample and improved measures$^{1.}$
Limited biomarker findings was attributed to small sample size$^1$. The literature provides an alternative view, as Osteoporosis Foundation (IOF) recommendations for biomarker testing intervals post intervention were not followed by this study i.e. 3–6 months (resorbtion) and 6 months (remodelling)$^8$.

### Conclusions

The conclusion that WBPA should be optimised during growth in T1DM for BMD to prevent osteoporosis in later life$^1$ was strongly supported by findings of large effect from this high quality study.
The study failed to provide evidence for use of biomarkers as a means of early detection for bone mineral change.

### Advice and Implications

This study confirms known relationships between WBPA and bone density. All children, including T1DM children at greater fracture risk due to Osteoporosis disease relationship, should be equally encouraged to engage in moderate intensity WBPA e.g. skipping, hopping, jumping of approximately 2 x 90 minutes weekly, to build BMD and counteract Osteoporosis risk$^{11}$.
Risk of adverse hypo/hyperglycaemic exercise related events can be effectively minimised with appropriate strategies.
Further research in accordance with IOF guidelines may determine biomarker usefulness as safer, early indicators of bone mineral change than DEXA scans for T1DM children.

### Resources/Further Information

* www.diabetes.co.uk
* www.osteoporosis.org.au/
* Bone Modelling and Remodelling
* Biochemical Markers of Bone Change
* Exercise and Osteoporosis fact sheet
* DEXA Scan
* Bikle DD. Vitamin D and Bone. Current Osteoporosis Reports. 2012;10(2):151-
* Mastrandrea LD, Wactawski-Wende J, Donahue RP, Hovey KM, Clark A, Quattrin T. Young women with type 1 diabetes have lower bone mineral density that persists over time. Diabetes Care. 2008;31.

### References

* Maggio ABR, Rizzoli RR, Marchand LM, Ferrari S, Beghetti M, Farpour-Lambert NJ. Physical Activity Increases Bone Mineral Density in Children with Type 1 Diabetes. Medicine and Science in Sports and Exercise. 2012;44(7):1206-11.
* PEDro, Physiotherapy Evidence Database[Internet]. Sydney:The George Institute for Global Health. 2016 [updated 2016 August 1: cited 2016 August 24]. Available from www.pedro.org.au
* Hoffmann T, Bennett S, Del Mar C. Evidence-based practice across the health professions. Chatswood, N.S.W: Elsevier Australia; 2013.
* Marieb EN, Hoehn K. Human anatomy & physiology. San Francisco, CA;London;: Benjamin Cummings; 2010.
* Brown MA, Duncan EL. Genetic studies of osteoporosis. Expert Reviews in Molecular Medicine.1(14):1-18.
* Leidig-Bruckner G, Grobholz S, Bruckner T, Scheidt-Nave C, Nawroth P, Schneider JG. Prevalence and determinants of osteoporosis in patients with type 1 and type 2 diabetes mellitus. BMC Endocrine Disorders. 2014;14(1):1-13.
* Vestergaard P, Rejnmark L, Mosekilde L. Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcif Tissue Int. 2009;84
* Čepelak I, Čvorišćec D. Biochemical markers of bone remodeling – review. Biochemia Medica 2009;19(1):17-35. http://dx.doi.org/10.11613/BM.2009.003
* Sealand R, Razavi C, Adler RA. Diabetes Mellitus and Osteoporosis. Current Diabetes Reports. 2013;13(3):411-8.
* Çamurdan MO, Ciaz P, BiDecl A, DemİRel F. Role of hemoglobin A1c, duration and puberty on bone mineral density in diabetic children. Pediatrics International. 2007;49(5):645-51.
* Osteoporosis Australia[Internet]. Sydney: Osteoporosis Australia; 2014 [last updated unknown; cited 2016 September 19]. Available from: .http://www.osteoporosis.org.au/sites/default/files/files/Exercise%20Fact%20Sheet%202nd%20Edition.pdf.