Background: Osteoporosis is a multifactorial disease characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture, leading to increased fracture risk. This study evaluated the biochemical, histological, and clinical parameters associated with osteoporosis and its progression. Methods: A cross-sectional study was conducted at Kabir Medical College, Peshawar, from ‘February 2022 to February 2023’. ‘A total of 120 participants’ were recruited and categorized into two groups based on their BMD (normal and low). Biochemical markers such as calcium, vitamin D, ‘alkaline phosphatase, and osteocalcin were measured.’ Histological analysis assessed trabecular bone volume, cortical thickness, and marrow adiposity, while clinical parameters, including lifestyle factors and inflammatory markers, were evaluated. Results: Participants with low BMD exhibited significantly lower calcium and vitamin D (p < 0.05) and elevated bone turnover markers, including alkaline phosphatase. Histological findings showed reduced trabecular bone volume and increased marrow adiposity in the low BMD group. Additionally, inflammatory markers such as interleukin-6 were significantly higher in this group. Postmenopausal women demonstrated a higher prevalence of low BMD, linked to reduced estrogen levels. Lifestyle factors such as smoking and physical inactivity were also more common among participants with low BMD. Conclusion: This study highlights the complex interplay between biochemical, histological, and clinical factors in osteoporosis development. Reduced calcium and vitamin D levels, increased bone turnover, and chronic inflammation are key contributors to decreased BMD. These findings emphasize the importance of early identification and targeted interventions to manage osteoporosis and prevent fractures.