Evidence of impaired bone quality in men with type 1 diabetes: a cross-sectional study

Objective: Type 1 diabetes (T1D) is associated with a substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have, however, not been uncovered. Men with TID seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D. Design and Methods: In this cross-sectional study, men with T1D and healthy, male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body), and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed. Results: Altogether, 33 men with T1D (43 ± 12 yrs) and 28 healthy male controls (42 ± 12 yrs) were included. Subjects with T1D exhibited lower whole body BMD than controls (p=0.04). TBS and BMSi were attenuated in men with T1D vs. controls (p=0.016 and p=0.004, respectively), and T1D subjects also had lower bone turnover. vs. controls. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD, but not with TBS or BMSi. Conclusions: This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, we confirm previous studies showing a modest decrease in BMD and low bone turnover in subjects with T1D, underscoring that bone should be recognized as a target of diabetic complications.

MO567PILOT STUDY OF BONE RESISTANCE MEASURED IN VIVO BY IMPACT MICROINDENTATION IN KIDNEY TRANSPLANTATION

Background and Aims Impact microindentation (IMI) is a new technique that measures bone material strength (BMS). Results are expressed as a BMS index (BMSi) which represents the ratio between the IMI distance [penetration of the needle-probe in patient’s bone (mid-shaft tibia)] versus a reference material (polimethylmethacrylate). Method Observational, prospective, single-center study. Baseline IMI (Osteoprobe®, Active Life Scientific, USA) and bone densitometry (iDXA, Lunar Health Care GE) were performed and data collected in the peritransplantation period of kidney transplant (KT) patients from May 2019 to May 2020, following our current clinical bone and transplant protocols. Based on the individual risk of fracture and current Spanish Society of Rheumathology/Nephrology guidelines, antirresorptive treatment (bisphosphonates or denosumab) was added on top of calcium and vitamin D supplements. We hereby present preliminary results of the control IMI performed 6 months after KT. Results Baseline IMI was performed in 45 patients, 62% men, 56±14 y/o, and a BMI of 24.9±3.5 kg/m2, reasonably controlled for classical serum bone mineral parameters. 70% were on dialysis prior to KT, 20% were diabetic, and 33.3% of women suffered from early menopause. 15.9% had a history of previous fragility fracture, 13% had a parent history of hip fracture, and 14% fell more than twice during the last year. Mean baseline FRAX® (https://www.sheffield.ac.uk/FRAX/tool.aspx?lang=sp) for a major osteoporotic fracture and hip were 4.3% and 2.3%, respectively. Baseline lumbar, femoral neck, hip and ultradistal radius DXA T-score were respectively -0.9, -1.7, -1.5, -2.0 SD. Mean BMSi was 78.5±7.6. Osteopenic/osteoporotic patients had a significantly lower BMSi than those who were not (76.3 vs 83; r = 0.37; p = 0.012). A statistically significant positive correlation was observed between BMSi and the trabecular bone score [(TBS), r = 0.346 ; p = 0.036). On a visual-analogic scale of pain, puncture was rated on average 1.1±1.6 over 10 (82% 0-2). 37.2% of patients began bisphosphonates (alendronic acid) and 9.3% denosumab. Control IMI was performed at 6 months in 24 patients, with a mean BMSi of 76.9±10.5. Mean difference between baseline and 6 months BMSi in this subgroup was 1.18±11.5. The group of patients treated with antiresorptives showed on average an increase in BMSi at 6 months, compared with a decrease in the control group (+5.2 vs -5.3; p = 0.054). Conclusion IMI is a technique with excellent tolerance that may offer complementary information on bone quality in the global assessment of bone resistance. IMI may allow the detection of EARLY changes in bone resistance in corticosteroid-treated KT patients with/without antiresorptives added to prophylactic treatment with calcium and vitamin D.

MO576ASSOCIATION OF BONE MATERIAL STRENGTH WITH BONE DENSITY IN PATIENTS WITH END-STAGE RENAL DISEASE

Background and Aims Patients with end-stage renal disease (ESRD) have an increased risk of skeletal complications, including an increased fracture risk, which is only partially identified by determination of bone mineral density (BMD). Experimentally, the complex bone-and mineral disorders in ESRD cause disturbances of bone material properties, but these have not been studied in vivo. Determination of bone material strength index (BMSi) by reference point indentation (RPI) is a novel method to determine bone material quality in vivo and can identify patients at increased fracture risk, even in the presence of normal BMD. We determined BMSi in ESRD patients and investigated its association with BMD and serum markers of mineral metabolism. Method 15 Adult patients with ESRD, scheduled for a living-donor kidney transplantation, were included in this cross-sectional study. Laboratory analyses included calcium, phosphate, PTH 1-84 and alkaline phosphatase. BMSi was determined by RPI with the OsteoProbe RUO in the tibia. Bone mineral density was measured by dual X-ray absorptiometry. Results Patients with bone mineral strenght index above median had higher bone mineral density of the right hip and total body than patients below median (p = 0.04). Alkaline phosphatase was lower in patients with BMSi below the median (47 (35-71) U/L vs. 103 (53-318) U/L, p = 0.009). There was a trend towards a significant relationship between length and BMSi (p = 0.09). Conclusion We identified for the first time an association of BMSi with BMD and alkaline phosphatase in patients with ESRD. Our findings of an association of BMSi with BMD are in accordance with findings in other populations with increased fracture risk.

Bone Material Strength index as measured by Impact Microindentation is low in Patients with Primary Hyperparathyroidism

Context In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well. Objective To evaluate bone material properties using Impact Microindentation (IMI) in PHPT patients. Methods In this cross-sectional study, Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender and fragility fracture status. Results Mean age of PHPT patients and controls was 61.8±13.3 and 61.0±11.8 years, respectively, p=0.77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92±0.15 vs 0.89±0.11, p=0.37) and the femoral neck (0.70±0.11 vs 0.67±0.07, p=0.15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2±5.7 vs 82.8±4.5, p<0.001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7±6.0 vs 79.6±5.0, p=0.015). Conclusion Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments.

Associations between Bone Material Strength Index, Calcaneal Quantitative Ultrasound and Bone Mineral Density in Men

Objectives Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. This study investigated how IMI is associated with calcaneal quantitative ultrasound and bone densitometry parameters in men. Methods BMSi was measured on the tibial plateau using the OsteoProbe in 377 men (ages 33-96yr) from the Geelong Osteoporosis Study. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were assessed at the calcaneus using an ultrasonometer. Areal BMD was measured at several skeletal sites using dual-energy X-ray absorptiometry. Linear associations between parameters were tested using Pearson’s correlation. Multivariable regression techniques were used to determine associations between BMSi and other measures of bone, independent of confounders. Results BMSi was negatively correlated with age (r = -0.171, p=0.001), weight (r = -0.100, p=0.052) and body mass index (r = -0.187, p=0.001), and positively with height (r = +0.109, p=0.034). There was some evidence to support a positive association between BMSi and BUA (β=0.052, p=0.037), SOS (β=0.013, p=0.144) and SI (β=0.036, p=0.051). After age adjustment, this association was attenuated. No correlations were observed between BMSi and BMD at any skeletal site (r-values ranged from -0.006 to +0.079, all p>0.13). Conclusion There was a small positive association between BMSi and QUS parameters, which were not independent of age. No associations were detected between BMSi and BMD. This suggests that BMSi and QUS are capturing common age-dependent properties of bone. Further research on the utility of IMI alone and complementary to conventional bone testing methods for predicting fracture risk is warranted.