Related Experiment Videos

Thiazolidinedione-induced skeletal fragility--mechanisms and implications

Andrew Grey1

  • 1Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz

Diabetes, Obesity & Metabolism
|August 2, 2008
PubMed

Insights

Type 2 diabetes mellitus (T2DM) increases fracture risk. Thiazolidinediones (TZDs) used for T2DM may worsen bone health by affecting bone formation and resorption, necessitating fracture risk assessment in patients.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Bone Biology

Background:

  • Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures.
  • Thiazolidinediones (TZDs), a class of drugs used to manage T2DM and insulin resistance, target PPAR-gamma.
  • PPAR-gamma is expressed in skeletal tissue and plays a role in bone metabolism.

Purpose of the Study:

  • To review the skeletal effects of thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus (T2DM).
  • To evaluate the impact of PPAR-gamma activation on bone formation and resorption.
  • To assess the clinical implications of TZD use on fracture risk in T2DM patients.

Main Methods:

  • Review of preclinical studies on PPAR-gamma activation and bone cell lineages.
  • Analysis of human studies investigating TZD effects on bone metabolism markers.
  • Examination of clinical data on bone mass and fracture rates in T2DM patients using TZDs.

Main Results:

  • Preclinical data show PPAR-gamma activation inhibits osteoblast differentiation and may enhance osteoclastogenesis.
  • Human studies indicate TZDs decrease bone formation markers, reduce bone mass, and elevate fracture rates, particularly in women.
  • Potential indirect adverse skeletal effects through modulation of hormones and cytokines.

Conclusions:

  • Thiazolidinedione (TZD) therapy in type 2 diabetes mellitus (T2DM) is associated with decreased bone formation, reduced bone mass, and increased fracture risk.
  • Fracture risk assessment is crucial for T2DM patients considered for TZD therapy.
  • Preventive strategies should be implemented for high-risk individuals.

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
Bone Disorders01:29

Bone Disorders

Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
Type I Diabetes III: Clinical Manifestations01:19

Type I Diabetes III: Clinical Manifestations

Type 1 diabetes mellitus typically presents with rapid-onset symptoms due to the body’s inability to utilize glucose in the absence of insulin. Since insulin is required for glucose uptake into cells, its deficiency leads to hyperglycemia and cellular energy deprivation, resulting in characteristic clinical features.Polyuria and PolydipsiaOne of the earliest, most prominent symptoms is polyuria (excessive urination). When blood glucose concentrations rise above the renal threshold, the kidneys...
Chronic Kidney Disease II: Clinical Manifestations01:24

Chronic Kidney Disease II: Clinical Manifestations

Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...