Shawn J. Yates

Diabetes mellitus is increasingly recognized as a disorder of skeletal quality in addition to metabolic dysregulation. Both type 1 and type 2 diabetes are associated with increased fracture risk, impaired fracture healing, and higher rates of orthopedic complications despite preserved or even elevated bone mineral density, highlighting the limitations of conventional densitometric assessment alone. Diabetic bone disease arises through complex and interconnected mechanisms involving osteoblast, osteocyte, and osteoclast dysfunction, accumulation of advanced glycation end products, oxidative stress, chronic inflammation, impaired insulin and insulin-like growth factor-1 signaling, and disruption of bone–pancreas and bone–adipose crosstalk. Here, we review the cellular, molecular, genetic, and epigenetic mechanisms that contribute to diabetic skeletal fragility and examine how these abnormalities impair bone remodeling, fracture healing, and orthopedic outcomes. Particular emphasis is placed on the disconnect between bone mineral density and bone quality, describing how alterations in bone microarchitecture and matrix integrity contribute to skeletal fragility beyond the conventional measures of bone mass. We further review emerging strategies for fracture risk assessment, including advanced imaging modalities and biomarkers that more accurately characterize diabetic bone disease, and discuss the influence of antidiabetic therapies, perioperative glycemic optimization, and emerging biologic and epigenetic therapeutic approaches on fracture healing and musculoskeletal outcomes. By integrating molecular mechanisms with clinical and orthopedic evidence, this review provides a comprehensive overview of diabetic bone disease while highlighting priorities for future research and clinical translation.

“Spinal cord stimulation (SCS)” is an established therapy for chronic pain and an emerging modality for functional recovery after spinal cord injury (SCI) and other clinical applications. Despite its clinical potential, current implantable SCS systems remain constrained by high power consumption, limited adaptability, device size, and long-term stability. Recent advances in closed-loop neuromodulation and integrated circuit (IC) design are enabling more adaptive, efficient, and miniaturized SCS systems. This narrative review focuses on integrated circuit and system-on-chip (SoC) architectures that enable more advanced closed-loop SCS modalities, including stimulation, sensing, and wireless power/data subsystems. Specifically, the present work examines stimulation drivers and charge-balancing circuits that ensure safe and precise current delivery, wireless power transfer, telemetry methods which maintain reliable energy and data flow in implanted systems, and analog front-end circuits that enable closed-loop biopotential monitoring for adaptive feedback control. It aims to highlight innovations in IC design, energy harvesting, and wireless communication strategies while discussing trade-offs in power efficiency, die area, thermal limits, and biocompatibility. Emerging trends emphasize miniaturized and adaptive neural implants that integrate circuit-level efficiency with therapeutic flexibility, thereby advancing the next generation of closed-loop neuromodulation technologies. Ultimately, innovations in microelectronics are paving the way for enhanced long-term efficacy, safety, and clinical applicability of implantable SCS systems to optimize functional impacts.