Osteoporosis is a chronic condition that causes bones to become thinner, more fragile, and more likely to break. It affects millions of people worldwide and becomes more common with age, particularly in postmenopausal women and older men. While current treatments can slow the progression of the disease, they cannot rebuild lost bone or fully reverse the damage. For this reason, regenerative medicine—specifically stem cell therapy—is emerging as a promising approach to managing and potentially treating osteoporosis.
In this review, Arjmand et al. explore how stem cells, particularly mesenchymal stem cells (MSCs), are being studied for their ability to restore bone strength and improve skeletal health in people with osteoporosis.
Understanding the Progression of Osteoporosis
Osteoporosis gradually weakens bones over time by reducing both their density and structural integrity. As bones lose mass, they become more brittle and prone to fractures. The condition is most often diagnosed in people over the age of 65, and the risk increases significantly after menopause due to a drop in estrogen levels.
The hip, spine, wrist, and shoulder are common fracture sites in individuals with osteoporosis. Among these, hip fractures are especially serious, often requiring hospitalization and long periods of rehabilitation. In some cases, these fractures can significantly reduce mobility and overall quality of life. With global life expectancy increasing, osteoporosis is becoming a major public health concern, creating both physical and economic burdens.
The Role of Bone Remodeling and How It Changes with Age
Bone tissue is constantly being broken down and rebuilt through a process known as bone remodeling. This cycle involves two types of cells: osteoclasts, which remove old or damaged bone, and osteoblasts, which generate new bone tissue. In healthy individuals, the activity of these cells is balanced, ensuring that bones remain strong and functional.
As people age, this balance often shifts. Osteoblasts become less active, producing fewer new bone cells, while osteoclasts continue breaking down old bone at a normal or accelerated rate. This leads to a gradual loss of bone mass and an increased risk of fractures.
Bone remodeling is influenced by various internal signaling molecules, including hormones, cytokines, and growth factors. These elements help regulate the function of bone cells, determining how much bone is built and how quickly it is resorbed. In people with osteoporosis, the signaling environment often favors bone loss over bone formation.
Diagnostic Tools and Treatment Limitations
Osteoporosis is most commonly diagnosed using dual-energy X-ray absorptiometry (DXA), a scan that measures bone mineral density (BMD). Results from this scan are given as T-scores, which compare a person’s bone density to that of a healthy 30-year-old adult. A T-score below -2.5 is considered diagnostic for osteoporosis, while scores between -1.0 and -2.5 indicate low bone mass, or osteopenia.
Current treatments for osteoporosis include both pharmacological and non-pharmacological approaches. Medications such as bisphosphonates, selective estrogen receptor modulators (SERMs), hormone therapy, denosumab, and parathyroid hormone analogs are commonly prescribed to reduce bone loss and lower the risk of fractures. In addition, nutritional support, physical exercise, and fall prevention strategies are recommended to help manage the condition.
Although these treatments can slow the progression of osteoporosis and reduce fracture risk, they do not reverse bone loss. Many medications also come with potential side effects, particularly when used long-term. This has created a need for more advanced and effective therapies capable of regenerating bone tissue and restoring skeletal strength.
Regenerative Medicine and the Promise of Stem Cells
In recent years, regenerative medicine has gained momentum as a potential solution for chronic diseases like osteoporosis. Stem cell therapy, in particular, offers a unique opportunity to not only halt bone loss but also encourage new bone formation. This represents a significant shift from simply managing the disease to actively repairing the damage it causes.
Mesenchymal stem cells (MSCs) are among the most studied types of stem cells for orthopedic and bone-related applications. Found in tissues such as bone marrow, adipose tissue, and umbilical cord tissue, MSCs have the ability to develop into several cell types, including osteoblasts—the bone-forming cells responsible for building new bone. These stem cells also release important signaling molecules that promote healing, reduce inflammation, and support tissue regeneration.
MSCs are considered ideal for therapeutic use because they are immune-privileged, meaning they are less likely to be rejected by the body, and they carry fewer ethical concerns compared to embryonic stem cells. Their ease of collection and expansion in the lab further enhances their clinical value.
The Mechanism of Stem Cell Action in Bone Repair
Bone formation involves two main processes: intramembranous ossification and endochondral ossification. Both rely on the activity of osteoblasts, and both can be influenced by MSCs. In intramembranous ossification, which forms flat bones such as those in the skull, MSCs directly convert into bone cells. In endochondral ossification, which forms long bones like the femur, cartilage is first created and then gradually replaced by bone. MSCs support both of these processes by providing the raw materials and signaling cues needed for effective regeneration.
In addition to becoming bone-forming cells, MSCs contribute to bone health through the release of growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-β). These molecules help coordinate the repair of damaged bone by stimulating cell growth, promoting blood vessel formation, and guiding the production of extracellular matrix—the material that gives bone its structure.
Stem cells also help rebalance the activity between osteoblasts and osteoclasts. In osteoporosis, where bone breakdown exceeds bone formation, MSCs can shift the system back toward growth by reducing osteoclast activity and encouraging osteoblast development. This dual action makes stem cell therapy particularly appealing as a comprehensive treatment for osteoporosis.
Emerging Therapies and Scientific Insights
Recent studies in animals and early-stage human trials have shown promising results for the use of MSCs in treating osteoporosis. These studies report improvements in bone density, strength, and healing time. In laboratory settings, MSCs have been shown to stimulate the growth of bone tissue and reduce inflammation, which is often elevated in individuals with bone loss.
Another emerging area of interest involves MSC-derived exosomes. These are tiny particles released by stem cells that carry the same regenerative molecules found in the cells themselves. Because exosomes can be isolated and administered without the need for transplanting whole cells, they offer a potentially safer and more targeted method of treatment.
The use of exosomes could allow for new forms of therapy that minimize immune reactions, simplify storage and transport, and avoid some of the challenges associated with live cell therapies. Early research suggests that exosome-based treatments may support bone remodeling, enhance blood supply, and reduce the severity of osteoporosis-related damage.
Future Directions in Osteoporosis Treatment
As regenerative medicine continues to evolve, future therapies for osteoporosis may include personalized stem cell treatments tailored to an individual’s genetic profile and bone health history. Scientists are also exploring the use of medications like oxytocin and parathyroid hormone to activate the body’s own stem cells and encourage bone regeneration from within.
Advancements in areas such as metabolomics—the study of small molecules in biological systems—may improve diagnosis and treatment selection for people at risk of osteoporosis. This could allow healthcare providers to better understand how a person’s metabolism affects bone loss and response to therapy.
Personalized medicine, which involves designing treatments based on an individual’s specific biological characteristics, is likely to play an increasing role in osteoporosis care. By combining genetic insights with regenerative therapies, it may be possible to offer more effective, targeted solutions for bone repair and long-term skeletal health.
Moving Toward Restoring Bone Health
Osteoporosis remains a significant health concern, particularly as the global population continues to age. While current treatments can slow its progression, they do not address the root cause of bone loss. Regenerative medicine offers a transformative path forward by focusing on rebuilding bone tissue rather than simply preserving what remains.
Mesenchymal stem cells have emerged as a leading option in the development of osteoporosis therapies. Their ability to both create new bone and modulate the biological environment around them makes them a powerful tool in the quest to restore bone health. Although more research is needed to refine treatment protocols and ensure safety, the future of stem cell therapy for osteoporosis is full of potential.
Source:
Arjmand B, Sarvari M, Alavi-Moghadam S, Payab M, Goodarzi P, Gilany K, Mehrdad N, Larijani B. Prospect of Stem Cell Therapy and Regenerative Medicine in Osteoporosis. Front Endocrinol (Lausanne). 2020 Jul 3;11:430. doi: 10.3389/fendo.2020.00430. PMID: 32719657; PMCID: PMC7347755.
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