Table 2.
Clinical evidences of metformin effects on bone
| Study design | Study population | n | Outcome | Ref. |
| Case control study | All subjects with bone fracture in Denmark (year 2000), vs 3-fold controls | 124655 fracture patients 373962 control | Fracture risk = 0.81 (95%CI: 0.70-0.93)1 (for metformin) | [59] |
| Cohort Study | Rochester residents first meeting Diabetes glycaemic criteria (1970-1994) | 1964 diabetic patients | Fracture risk = 0.7 (95%CI: 0.6-0.96)2 (for metformin) | [6] |
| Case control study | A study nested within a cohort of 1945 diabetic Tuscany outpatients (1998-2004) | 83 fracture patients 249 control | Fracture risk = 0.60 (95%CI: 0.34-1.08)3 (for metformin) | [60] |
| Double-blind, randomized, controlled clinical trial | Recently diagnosed, drug-naïve patients with type 2 diabetes, treated for a median of 4 yr with rosiglitazone, metformin, or glyburide | Rosiglitazone: n = 1456; Metformin: n = 1454; Glyburide: n = 1441 | Nº Fractures (%): Rosiglitazone 60 (9.30) Metformin 30 (5.08)4 Glyburide 21 (3.47)4 | [12] |
| Double-blind, randomized, controlled clinical trial | Recently diagnosed, drug-naïve patients with type 2 diabetes, treated for a median of 4 yr with RSG, MET, or GLY | Paired baseline and 12-mo stored serum samples from 1605 patients | In women, CTX increased by 6.1% with RSG, decreased by 1.3% with MET (P = 0.03) In men, CTX was unchanged on RSG (-1.0%) and fell with MET -12.7% (P = 0.001) | [61] |
| Randomized, parallel group, double-blind, multicentre study | Drug naïve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus | 688 patients equally randomized to RSG/MET or MET | BMD at week 80: Lumbar = (-2.2) (95%CI: -3.5, -0.9) Total hip = (-1.5) (95%CI: -2.3, -0.7)5 | [62] |
| Prospective randomized study with active comparator study | Forty postmenopausal diabetic women recruited from Tanta University Hospitals | 20 patients on metformin and 20 on sitagliptin, for 12 wk | BMD was unchanged in both groups at week 12 Bone turnover markers remained unchanged from baseline in MET | [63] |
| Prospective randomized double-blind, double-dummy with active comparator | Men with uncomplicated type 2 diabetes mellitus, aged 45-65 yr | 71 men were randomized to PIO once daily or MET twice daily | Sclerostin levels at week 24 increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (P = 0.018) | [64] |
Relative risk of any fracture interpreted as OR with 95%CI for several variables in the population of Denmark (National Health Registry, year 2000);
Multivariate HR for the development of any new fracture among 1964 Rochester, MN, United States residents after recognition of diabetes mellitus in 1970-1994;
Exposure for at least 36 mo to hypoglycemic treatments in case subjects and matched control subjects, interpreted as OR with 95%CI;
P < 0.01 for comparison of fracture risk in women with rosiglitazone (unadjusted, contingency χ2 test);
Percentage of change in BMD at week 80, comparing RSG/MET vs MET. RSG: Rosiglitazone; MET: Metformi; GLY: Glyburide; PIO: Pioglitazone; BMD: Bone mineral density; OR: Odds ratio; HR: Hazard ratios.