Ensayos clínicos

Inclusion Criteria:

• Women and men ≥ 50 years old without a history of fragility fracture.
• All women will be postmenopausal (serum follicle stimulating hormone [FSH] > 20 IU/L). 
• All T2DM subjects will be defined as having a hemoglobin A1c level ≥ 6.5% within the past 5 years per the American Diabetes Association; matched non-diabetic controls will be defined as having a hemoglobin A1c < 5.7% (28)]. 
• Subjects with fractures only of the skull and face, hands and fingers, feet and toes, patella, and ankle, sites which are not closely associated with BMD in most studies, are eligible for inclusion. 

Exclusion Criteria:

• Non-vertebral fragility fracture subjects as those having had one of the following fractures which are clearly associated with low BMD and occur at sites with substantial amounts of cortical bone (in contrast to the vertebrae, which have an extremely thin cortical shell following mild to moderate trauma (i.e., in the course of daily activities or falls from standing height or less within the previous 10 years:
  • proximal femur;
  • proximal humerus;
  • distal forearm;
  • other femoral sites (e.g., shaft);
  • other upper extremity sites (but excluding hands and fingers):
    • pelvis, ribs, clavicle, scapula, sternum, and tibia/fibula (but excluding ankle fractures, which are not associated with BMD).
• Anyone with pathological fractures (e.g., malignancy) will be excluded.  
• Morbid obesity (BMI ≥ 40 kg/m²).
• Significant abnormality in any of the screening laboratory studies.
• Presence of stage IV or V chronic kidney disease, chronic liver disease, severe neuropathic disease, unstable cardiovascular disease, malignancy, chronic gastrointestinal disease, autoimmune rheumatologic conditions (e.g., rheumatoid arthritis), hypo- or hyperparathyroidism, Cushing’s syndrome, severe chronic obstructive pulmonary disease, alcoholism, or type 1 diabetes.
• Significant skin disease, bruising, local edema, or infection over the microindentation site (anterior tibia)
• Treatment with any of the following drugs: oral corticosteroids (inhaled corticosteroids ok for inclusion)  (>3 months at any time or >10 days within the previous year).
• Treatment within the past year with any of the following: anticonvulsants (except gabapentin as it has no effect on bones, pharmacological doses of thyroid hormone (causing thyroid stimulating hormone [TSH] decline below normal), adrenal or anabolic steroids, aromatase inhibitors, calcitonin, estrogen (E), selective E receptor modulators (SERMs), parathyroid hormone (PTH), denosumab, or thiazolidinediones. 
• Undergoing treatment for blood clots, coagulation defects, or treatment with any of the following drugs: oral corticosteroids (inhaled corticosteroids ok for inclusion)  (>3 months at any time or >10 days within the previous year).
• Treatment within the past year with any of the following: anticonvulsants, pharmacological doses of thyroid hormone (causing thyroid stimulating hormone [TSH] decline below normal), adrenal or anabolic steroids, aromatase inhibitors, calcitonin, estrogen. 
• Selective E receptor modulators (SERMs), parathyroid hormone (PTH), denosumab, or thiazolidinediones.  
• Subjects who have been exposed to a bisphosphonate within the past 5 years.
• All subjects will be required to have sufficient levels of vitamin D (serum 25-hydroxyvitamin D [25-(OH)D] >15 ng/ml) to exclude patients who may have osteomalacia. 
• Subjects will be required to provider a complete list of current and past medications, including the duration and dose of diabetic medications.