Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates.

The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology, and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0%-6.5% higher at all sites (all p<.005) in T2DM vs controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3%-6.4%) and number (3.8%-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM vs controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2%-8.5% lower adjusted aBMD at all sites by DXA compared with those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2%-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1 and 17.2% lower failure load at the radius and tibia, respectively (all p<.05); plate volume and thickness were 5.7% and 4.7% lower, respectively, (p<.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p=.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load.

Reasons for increased fracture risk in type 2 diabetes (T2DM) are not well-understood. We used a multi-ethnic, population-based cohort (n = 565), to study bone structure in women with T2DM (n = 175) using advanced imaging and analysis techniques. Participants with T2DM tended to have higher bone density and better structure by DXA and HRpQCT, respectively, at the radius and tibia; only cortical porosity was higher (worse) in participants with diabetes compared with those without diabetes but there was no difference in bone strength. Participants with T2DM and fracture had lower cortical parameters and bone strength compared with participants with T2DM without fracture at both sites. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits associated with lower failure load.

Bisphosphonates Maintain BMD after Sequential Teriparatide and Denosumab in Premenopausal Women with Idiopathic Osteoporosis.

CONTEXT: We previously reported that sequential teriparatide followed by denosumab substantially increases BMD in premenopausal idiopathic osteoporosis (PremenIOP). OBJECTIVE: To determine whether administration of bisphosphonates after denosumab cessation is associated with stable BMD in PremenIOP. DESIGN: Open-label extension study. PARTICIPANTS: 24 PremenIOP Teriparatide-Denosumab Study participants. INTERVENTIONS: Oral alendronate (ALN), 70mg weekly, or IV zoledronic acid (ZOL), 5mg once (patient choice), was administered 7 months (M) after final denosumab dose. OUTCOMES: BMD by DXA and serum C-telopeptide (CTX) q6M; vertebral fracture assessment (VFA) and HR-pQCT q12M. RESULTS: 24 women with PremenIOP (aged 43 ± 8 years), severely affected with low trauma adult fractures (range 0-12; 9 with vertebral fractures) and/or very low BMD, had large BMD increases on sequential teriparatide-denosumab (spine: 25 ± 9%; total hip: 11 ± 6%). During the Bisphosphonate Extension, mean BMD and CTX changes in the entire group were small and not statistically significant at 6 or 12M.Women choosing ZOL (n = 6) versus ALN (n = 18) did not differ by baseline age, BMI, fractures, BMD, or CTX. On ZOL, there were small LSBMD declines and CTX increases, particularly between 6M and 12M, while greater stability was observed on ALN.Changes in BMD and CTX did not differ by duration of denosumab (36M vs <36M) or between 20 women who remained premenopausal and 4 who transitioned into menopause. Higher pre-teriparatide CTX, likely reflecting baseline remodeling status, predicted more spine and hip bone loss. No new vertebral (clinical or VFA screening) or non-vertebral fractures occurred. CONCLUSION: BMD remained stable in women with PremenIOP who received bisphosphonates after sequential teriparatide-denosumab therapy.