Bone Mineral Is More Heterogeneously Distributed in the Femoral Heads of Osteoporotic and Diabetic Patients: A Pilot Study

Abstract

Osteoporosis is associated with systemic bone loss, leading to a significant deterioration of bone microarchitecture and an increased fracture risk. Although recent studies have shown that the distribution of bone mineral becomes more heterogeneous because of estrogen deficiency in animal models of osteoporosis, it is not known whether osteoporosis alters mineral distribution in human bone. Type 2 diabetes mellitus (T2DM) can also increase bone fracture risk and is associated with impaired bone cell function, compromised collagen structure, and reduced mechanical properties. However, it is not known whether alterations in mineral distribution arise in diabetic (DB) patients' bone. In this study, we quantify mineral content distribution and tissue microarchitecture (by μCT) and mechanical properties (by compression testing) of cancellous bone from femoral heads of osteoporotic (OP; n = 10), DB (n = 7), and osteoarthritic (OA; n = 7) patients. We report that though OP cancellous bone has significantly deteriorated compressive mechanical properties and significantly compromised microarchitecture compared with OA controls, there is also a significant increase in the mean mineral content. Moreover, the heterogeneity of the mineral content in OP bone is significantly higher than controls (+25%) and is explained by a significant increase in bone volume at high mineral levels. We propose that these mineral alterations act to exacerbate the already reduced bone quality caused by reduced cancellous bone volume during osteoporosis. We show for the first time that cancellous bone mineralization is significantly more heterogeneous (+26%) in patients presenting with T2DM compared with OA (non-DB) controls, and that this heterogeneity is characterized by a significant increase in bone volume at low mineral levels. Despite these mineralization changes, bone microarchitecture and mechanical properties are not significantly different between OA groups with and without T2DM. Nonetheless, the observed alterations in mineral heterogeneity may play an important tissue-level role in bone fragility associated with OP and DB bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Keywords: DIABETES; MECHANICAL PROPERTIES; MICROARCHITECTURE; MINERAL HETEROGENEITY; OSTEOARTHRITIS; OSTEOPOROSIS.

Figure 1

Femoral heads were cut into cuboid cores for μCT scanning and compression testing. Only cores from the central region (yellow box) were analyzed for each femoral head.

Figure 2

Microarchitecture. 3D‐volume renderings from μCT scans of (A) OA, (B) DB, and (C) OP bone. Box and whisker plots showing (D) bone volume fraction (BV/TV), (E) trabecular thickness (Tb.Th, mm), (F) trabecular number (Tb.N, mm^‐1), (G) trabecular spacing (Tb.Sp, mm) for each patient group: OA (n = 7), DB (n = 7), and OP (n = 10). * Indicates significance (p < 0.05). OA = osteoarthritis; DB = type 2 diabetes mellitus; OP = osteoporosis.

Figure 3

Mechanical data. (A) Loading curves representative of each patient group. Apparent strength (σmax) = maximum stress experienced during testing. Slope of the loading curves were used to estimate apparent stiffness. Box and whisker plots showing (B) apparent stiffness, (C) apparent strength, (D) energy to failure, and (E) post‐yield energy for each patient group. Energy to failure was estimated from the area under the loading curve from 0.01 strain to strain at maximum stress. Post‐yield energy was estimated by calculating the area under the loading curve after maximum stress (areas under the OP curve highlighted above). For consistency, this figure was then normalized by the strain experienced (in the above case [0.06–0.05 = 0.01 strain]). OA (n = 7), DB (n = 7), and OP (n = 10). * Indicates significance (p < 0.05). OA = osteoarthritis; DB = type 2 diabetes mellitus; OP = osteoporosis.

Figure 4

Mineral data. (A) Representative bone mineral density distribution (BMDD) for OA, DB, and OP bone. A histogram of % bone volume (BV) is plotted as a function of mineral content (mg HA/cm³) derived from gray‐scale values in the CT image. Histogram bin width = 9.5 mg HA/cm³. Full‐width at half‐maximum (FWHM) indicates mineral heterogeneity. FWHM is smallest for OA patients, indicating relatively homogeneous mineral content, compared with DB and OP patients. The peak (“mode”/most frequent value) for OP is shifted to the right, indicating a more highly mineralized tissue. Box and whisker plots show (B) mineral heterogeneity as indicated by FWHM, (C) mode mineral content, and (D) mean mineral content. Vertical lines in (A) define “lower” (<700 mg HA/cm³) and “higher” (>1000 mg HA/cm³) thresholds that were analyzed for each bone core. Percentages of bone volume at lower and higher levels are plotted in (E) and (F), respectively. In the graphs shown, DB shows significantly increased levels of lower mineralization compared with OP (E), while OP has significantly increased levels of higher mineralization compared with DB and OA (F). OA (n = 7), DB (n = 7), and OP (n = 10). * Indicates significance (p < 0.05). OA = osteoarthritis; DB = type 2 diabetes mellitus; OP = osteoporosis.