Bone weakening is a critical health concern that is seen in multiple conditions, such as osteoporosis and other genetically driven diseases, poor nutrition, and bone cement implantation syndrome. The bone is a hierarchical composite material predominantly composed of mineral crystals, collagen matrix, and water. The ductile collagen phase, brittle hydroxyapatite mineral crystals, and water are organized to create a structure that is both tough and lightweight. To halt the various conditions that lead to bone weakening, the intricate mechanics of bone deformation and failure at the molecular scale must be understood.1
Osteoporosis is characterized by reduced bone mineral density (BMD) that leads to weakened bones and carries a high fracture risk. In a study published by Koidou et al., it was shown that DXA scans, a bone density test, can detect osteopenia – bone density loss that often precedes osteoporosis. This test indicates a critical window for preventive intervention by clinicians. Nutritional deficiencies also exacerbate bone diseases because calcium and vitamin D are needed for bone remodeling and mineralization processes. Inadequate intake of these vital nutrients compromises bone mineral density (BMD) and microarchitectural deterioration. Finally, genetic factors can predispose individuals to osteoporosis as well as other serious diseases that affect bone collagen production or mineral density to create an innate susceptibility to fracture and structural weakness. 1,2,3
While osteoporosis is predominantly seen in the elderly, osteogenesis imperfecta (OI), a monogenic disorder, manifests in childhood. OI has been linked to mutations in the genes that code for collagen type I alpha chains, COL1A1 or COL1A2. These mutations disrupt the structural integrity of collagen, thereby compromising bone strength and leading to increased fragility. OI mutations also impact the various components involved in the biosynthesis and transport of collagen within cellular structures, such as the endoplasmic reticulum and Golgi organelle. 4,5
Other genetically driven conditions that cause bone weakening include familial hypocalciuric hypercalcemia (FHH) and hypophosphatasia. According to Hannan et al., FHH often arises from mutations in genes such as CASR, GNA11, or AP2S1, which are responsible for calcium-sensing receptor regulation. These genetic anomalies cause altered calcium metabolism, leading to abnormal bone remodeling processes. Similarly, hypophosphatasia results from defects in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNAP), a critical enzyme in bone mineralization pathways. By leveraging advanced genetic screening techniques and molecular insights, clinicians can better predict susceptibility, optimize therapeutic interventions, and potentially mitigate the progression of these debilitating bone diseases through targeted molecular therapies.6
In advanced cases of bone disease, like osteoporosis, bone cement is used to repair fractures caused by weakened bone. However, the material used to stabilize fractures or replace joints introduces a mechanical stressor that can exacerbate existing symptoms since the bone scaffold is very fragile and can cause complications during the procedure, such as hypoxia and postoperative confusion. BCIS emphasizes the importance of improving screening tests like DXA and genetic screening to enhance clinical foresight in bone diseases characterized by progressive bone weakening. 3 Prevention and early treatment of bone weakening is critical.
References
1. Eirini, Koidou, et al. “Bone Density Measurements and Biomarkers in Nutrition: DXA (Dual X-ray Absorptiometry), Osteopenia, and Osteoporosis.” *Biomarkers in Nutrition*, edited by V.B. Patel and V.R. Preedy, Springer Nature Switzerland AG, 2022, pp. 1-19.
2. Verma, Akarsh, and Shigenobu Ogata. “Computational Modelling of Deformation and Failure of Bone at Molecular Scale.” *Forcefields for Atomistic-Scale Simulations: Materials and Applications*, edited by A. Verma et al., Lecture Notes in Applied and Computational Mechanics, vol. 99, Springer Nature Singapore Pte Ltd., 2022, pp. 253-268. https://doi.org/10.1007/978-981-19-3092-8_13.
3. Joury, Lou’i Basil, et al. “Bone Cement and Its Anesthetic Complications: A Narrative Review.” *Journal of Clinical Medicine*, vol. 12, no. 6, 2023, p. 2105, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056839/.
4. Tauer, J. T., Robinson, M.-E., & Rauch, F. (2019). Osteogenesis imperfecta: New perspectives from clinical and translational research. *JBMR Plus*, 3(8), e10174. https://doi.org/10.1002/jbm4.10174
5. Storoni, S., Eekhoff, M., Elting, M., Wissel, L., Pals, G., Claeys, L., Bravenboer, N., Maugeri, A., & Micha, D. (2021). Collagen transport and related pathways in Osteogenesis
Imperfecta. *Human Genetics*, 140(7), 1121-1141. https://doi.org/10.1007/s00439-021-02302-2
6. Hannan, F. M., Newey, P. J., Whyte, M. P., & Thakker, R. V. (2019). Genetic approaches to metabolic bone diseases. *British Journal of Clinical Pharmacology*, 85(6), 1147-1160. https://doi.org/10.1111/bcp.13800