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Objective: Osteolysis and low bone mineral density (BMD) are underappreciated consequences of several chronic diseases that may elevate the risk for fracture. The purpose of this study was to assess tarsal BMD associated with acute inflammation (ie, inflammatory osteolysis) in individuals with chronic diabetes mellitus (DM), peripheral neuropathy (PN), and recent-onset neuropathic (Charcot) arthropathy (NCA) of the foot. Research Design and Methods: This was a case-control study of 32 people (11 men, 21 women) with DM, PN, and NCA of the foot or ankle. The subjects with DM, PN, and NCA were compared with 64 age-, sex-, and race-matched control subjects (24 men, 40 women) without DM, PN or NCA. Within the first 3 weeks of cast immobilization, BMD was estimated in both calcanei using quantitative ultra- sonometry. Acute inflammation was confirmed by comparing skin temperature differences between the feet of the subjects with DM, PN, and NCA and the feet of the control subjects. Results: Skin temperature differences averaged 6.7oF (SD=4.0oF) (involved foot minus noninvolved foot) in the feet of the subjects with DM, PN, and NCA compared with 0.0oF (SD=1.3oF) in the feet of the control subjects. Calcaneal BMD averaged 384 mg/cm2 (SD=110) in the involved feet and 467 mg/cm2 (SD=123) in the noninvolved feet of the subjects with DM, PN, and NCA and 545 mg/cm2 (SD = 121) in combined right and left feet of the control subjects. Conclusions: Inflammation in individuals with DM, PN, and NCA may contribute to or exacerbate a rapid loss of BMD. Inflammatory osteolysis may be a prominent factor responsible for both the spontaneous onset of neuropathic fracture and the insidious and progressive foot deformity that is the hallmark of the chronic Charcot foot [ABSTRACT FROM AUTHOR]

Metatarsals are frequent sites of stress and fragility fractures in younger athletic populations and aging older adults. Metatarsal fractures are particularly common in Charcot neuroarthropathy (CN), a complication of diabetes mellitus (DM) and peripheral neuropathy (PN). Neuropathic metatarsal fractures may be caused by an accelerated cortical bone osteolysis and may be reflected as geometric‐derived strength estimates from standard foot radiographs. The purpose of this cross‐sectional study was to determine geometry and strength‐derived estimates of the metatarsals in individuals with DM, PN, and CN compared with younger and older adult controls who were nondiabetic and nonneuropathic. We studied 62 participants: 20 young adult controls (YACs), 22 older adult controls (OACs), and 20 diagnosed with DMPN&CN. From weight‐bearing radiographs, we measured the outer diaphysis diameter and inner marrow diameter at the distal, middle, and proximal diaphysis sites of the second and fifth metatarsal. From these diameters, we derived strength estimates of combined cortical width (CCt.Wi), percent cortical area (%Ct.rA), buckling ratio (BR), moment of inertia (MOI), and section modulus (SM) at each site in both metatarsals. DMPN&CN participants had an accelerated cortical thinning, decreased %Ct.Ar, increased BR, and lower MOI and SM compared with OACs and YACs. The OACs showed age‐related decreases in CCt.Wi and % Ct.Ar, and increased BR. The BR demonstrated significant group × bone × site interaction with the distal fifth metatarsal in the DMPN&CN group having the lowest bone strength. The BR in the distal fifth metatarsal of DMPN&CN participants was 36% and 49% greater than in the OAC and YAC groups, respectively. DMPN&CN participants have lower metatarsal bone strength estimates compared with younger and older adult controls. Standard foot radiographs demonstrate an accelerated cortical osteolysis in DMPN&CN individuals, particularly in the distal fifth metatarsal diaphysis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand the magnitude of pedal osteolysis after immobilization and the time course for recovery. Objective To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33–53 weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA). Methods Fifty-five participants with peripheral neuropathy were studied. Twenty-eight participants had NPU and 27 participants had CNA. Bilateral foot skin temperature was assessed before immobilization and bilateral calcaneal BMD was assessed before immobilization, after immobilization and after recovery using quantitative ultrasonometry. Results Before immobilization, skin temperature differences in CNA between their index and contralateral foot were markedly higher than NPU feet (3.0 degree C versus 0.7 degree C, respectively, p < 0.01); BMD in NPU immobilized feet averaged 486 ± 136 mg/cm 2 , and CNA immobilized feet averaged 456 ± 138 mg/cm 2 , p > 0.05). After immobilization, index NPU feet lost 27 mg/cm 2 ; CNA feet lost 47 mg/cm 2 of BMD, p < 0.05. After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic. Conclusions There was a greater osteolysis after immobilization with an attenuated recovery in CNA feet compared to NPU feet. The attenuated recovery of pedal BMD in CNA feet resulted in a greater percentage of feet classified as osteoporotic and osteopenic. [ABSTRACT FROM AUTHOR]

Abstract: Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus (DM) and peripheral neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture. We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density (BMD) and geometric strength indices using volumetric quantitative computed tomography. Twenty individuals with DM+PN were compared to twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals. Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM+PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet. There was a non-significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM+PN and CN subjects despite the CN group''s significantly lower BMD. Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively. In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury rather than increased fracture resistance. Future research using these techniques will aid further understanding of the inflammation-mediated bony changes associated with development and progression of CN and other diseases. [Copyright &y& Elsevier]