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Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus

Mansur SA, Mieczkowska A, Bouvard B, Flatt PR, Chappard D, Irwin N, et al.

J Cell Physiol, 2015 Dec;230(12):3009-18.
PMID: 26016732 DOI: 10.1002/jcp.25033

Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.

Matched MeSH terms: Bone Remodeling/drug effects
Transplantation of human dental pulp stem cells: enhance bone consolidation in mandibular distraction osteogenesis

Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH

J Oral Maxillofac Surg, 2013 Oct;71(10):1758.e1-13.
PMID: 24040948 DOI: 10.1016/j.joms.2013.05.016

The main aim of the present study was to evaluate the capacity of stem cells from human exfoliated deciduous teeth (SHED) to enhance mandibular distraction osteogenesis (DO) in rabbits.

Matched MeSH terms: Bone Remodeling/physiology
The effects of TNF α antagonist therapy on bone metabolism in rheumatoid arthritis: a systematic review

Sakthiswary R, Das S

Curr Drug Targets, 2013 Dec;14(13):1552-7.
PMID: 23848441

Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.

Matched MeSH terms: Bone Remodeling/drug effects
Bone health among patients with primary aldosteronism: a systematic review and meta-analysis

Loh HH, Yee A, Loh HS

Minerva Endocrinol., 2019 Dec;44(4):387-396.
PMID: 30482008 DOI: 10.23736/S0391-1977.18.02867-5

INTRODUCTION: Recent studies showed a possible association between hyperaldosteronism and secondary hyperparathyroidism leading to reduced bone health, however results are conflicting.
EVIDENCE ACQUISITION: We conducted a meta-analysis to evaluate the relationship between primary aldosteronism (PA) with bone biochemical markers and to assess bone mineral density in patients with primary aldosteronism.
EVIDENCE SYNTHESIS: A total of 939 subjects were examined (37.5% with PA). Patients with PA had significantly higher serum parathyroid hormone, lower serum calcium, higher urine calcium excretion and higher serum alkaline phosphatase compared to patients without PA, with no significant difference in serum vitamin D between both groups. Bone mineral density of lumbar spine, femoral neck and total neck of femur were similar between two groups. With PA treatment, there was a significant increment in serum calcium and reduction in serum parathyroid hormone.
CONCLUSIONS: PA is associated with hypercalciuria with subsequent secondary hyperparathyroidism. This potentially affects bone health. We recommend this to be part of complication screening among patients with PA.

Matched MeSH terms: Bone Remodeling