As China's population ages increasingly, osteoporosis has emerged as a severe public health concern. Bone mineral density (BMD), which indirectly reflects the health status of bones, is a crucial indicator of bone strength. BMD serves as a diagnostic criterion for osteoporosis, as decreased bone strength leads to an elevated risk of fractures. BMD is influenced by various factors, including genetics, endocrinology, diet, and exercise. With advancing age, there is an increased loss of bone minerals in middle-aged and elderly individuals, and menopause in women also contributes to decreased bone mineral density. In clinical practice, BMD is often addressed through treatments such as chemical medications, hormones, and traditional Chinese medicines. These treatments aim to increase bone density by mechanisms like enhancing calcium content, elevating estrogen levels in patients, inhibiting osteoclast-secreted cytokines to reduce bone resorption, promoting osteoclast apoptosis, and increasing osteoblast activity.

The pathogenesis of osteoporosis primarily encompasses cellular and signaling pathway levels. In most cases, there exists a dynamic balance between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disruption of this balance leads to the development of osteoporosis. Within the bone microenvironment, osteoclasts are formed from hematopoietic stem cell-derived multinucleated cells under the mediation of receptor activator of nuclear factor-κB ligand (RANKL). Osteoblasts, mostly differentiated from bone marrow mesenchymal cells, along with osteocytes and osteoclasts, play vital roles in the progression of osteoporosis. A significant reduction in estrogen levels can trigger osteocyte apoptosis, contributing to the onset of osteoporosis. Osteoblast apoptosis is associated with Fas/Fas-L, and tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) can induce osteoblast apoptosis. Abnormal osteoblast apoptosis is a crucial mechanism in the pathogenesis of osteoporosis. Specifically, IL-1 decreases caspase levels in osteoclasts, activates the NF-κB pathway, stimulates osteoclast proliferation, and disrupts the homeostasis between bone resorption and bone formation, ultimately leading to osteoporosis.

The Osteoprotegerin/Receptor Activator of Nuclear Factor-κB (RANK)/RANK Ligand (RANKL) signaling pathway (OPG/RANK/RANKL) plays a significant regulatory role in bone remodeling and bone development. It has been reported that Tenghuang Jiangu Capsule can regulate the OPG/RANK/RANKL axis, thereby modulating calcium and phosphorus metabolism and the biomechanical properties of the femur in rats with ovariectomized osteoporosis. The Wnt/β-catenin pathway is crucial in bone remodeling, cell growth, development, and apoptosis. Activation of the Wnt/β-Catenin signaling pathway in osteocytes has been reported to promote osteogenic differentiation of bone marrow stromal cells (BMSCs) through upregulation of Notch signaling, which in turn inhibits the occurrence of osteoporosis.

Currently, drug therapy is the primary approach in the clinical treatment of osteoporosis, and it has achieved certain therapeutic effects. Common medications used include estrogen-based drugs, calcitonin, bisphosphonates, and traditional Chinese medicines.

1. Estrogen-based Drugs

Bone is a target tissue for estrogens, which exert direct effects on bone tissue. Estrogens can induce apoptosis in bone cells, promote the proliferation and differentiation of osteoblasts, and regulate bone formation and resorption processes. Furthermore, estrogens mediate through the paracrine signaling system of osteoblasts to reduce osteoclast activity, thereby participating in bone resorption. According to reports, the combined use of conjugated equine estrogen and medroxyprogesterone acetate can improve bone mineral density (BMD) and prevent osteoporotic fractures. Estradiol valerate combined with alendronate is effective in improving postmenopausal osteoporosis. Estrogen-based drugs are widely recognized as first-line medications for the clinical treatment of osteoporosis. However, their high hepatobiliary clearance rate, low absorption rate, and some adverse reactions hinder their widespread use.

2.Calcitonin

Calcitonin is a single-chain polypeptide. According to reports, salmon calcitonin injections combined with Bushen Jiangu Decoction (a traditional Chinese medicinal formula for nourishing the kidneys and strengthening bones) have shown significant effects in treating postmenopausal osteoporosis and improving bone mineral density (BMD) in patients. Additionally, calcitonin gene-related peptide (CGRP) plays an important role in bone growth and repair processes. However, some patients may experience allergic reactions and gastrointestinal adverse effects after using calcitonin.

3.Bisphosphonate Drugs

Bisphosphonate drugs are relatively stable and can bind to bone mineralized matrix, inhibiting bone resorption, increasing bone mass, and subsequently improving bone mineral density (BMD) in patients. According to reports, the combined use of calcitriol and bisphosphonate drugs in the treatment of osteoporosis is safe, more effective, and widely used in clinical practice. Clinically, alendronate has been shown to effectively improve postmenopausal osteoporosis in women. However, bisphosphonate drugs may cause adverse reactions such as fever after injection.

4.Calcium Supplements and Vitamins

Vitamin D is a steroid hormone, and the combination of calcium supplements and vitamin D has a relatively well-established role in the treatment of osteoporosis, offering good therapeutic effects. However, oral administration of calcium supplements and vitamin D may cause gastrointestinal discomfort, kidney stones, and cardiovascular adverse events. Long-term use of calcium supplements and vitamins by patients may lead to adverse reactions such as hypercalcemia and urinary stones.

5.Parathyroid Hormone (PTH)

Parathyroid hormone (PTH) is a single-chain polypeptide secreted by the chief cells of the parathyroid glands. By enhancing DNA repair and inhibiting osteoblast apoptosis, PTH can increase bone mineral density (BMD) in patients with osteoporosis, improve bone metabolism indicators, and has good safety, making it a valuable treatment option. However, long-term use of PTH may cause enhanced bone resorption and bone loss in patients.

6.Chinese Medicinal Herbs for Increasing Bone Density

Chinese medicine also plays a significant role in preventing and treating reduced bone density. Studies have found that herbs such as Epimedium brevicornum, Psoralea corylifolia, and Eucommia ulmoides exhibit effects in improving bone microstructure and enhancing bone biomechanical properties. Current clinical research on Epimedium brevicornum reveals that it reduces osteoclast activity by lowering serum levels of PINP (Procollagen Type I N-terminal Propeptide) while simultaneously increasing the β-CTX (Type I Collagen Carboxyterminal Telopeptide β-special sequence) marker. The total flavonoids of Epimedium brevicornum may prevent and treat osteoporosis by promoting osteoblast differentiation and proliferation, with hormone-like effects. Icariin, a major component of Epimedium, stimulates bone cells to secrete calcitonin, increases the number of calcified nodules, promotes chondrocyte differentiation and proliferation while inhibiting excessive apoptosis, regulates proteins related to cellular metabolism, effectively protects cartilage, and makes bones stable and strong. Furthermore, icariin inhibits osteoclast differentiation by suppressing the expression of osteoclast fusion proteins in the body.

Currently, there is a wide variety of drugs commonly used in clinical practice for the treatment of osteoporosis. Although these drugs have demonstrated certain efficacy, they may also cause adverse reactions. Therefore, the screening and development of novel, safe, and effective drugs for the treatment of osteoporosis remains a crucial task for clinicians and pharmaceutical researchers.

References:

[1] Zhang Wenjing. Research Progress in Osteoporosis Treatment [J]. Chinese Journal of Geriatric Health Care, 2020, 18(04): 101-102.

[2] Sa Yi. Patterns in the Formulation of Health Food for Increasing Bone Density and Suggestions for Regulatory Research and Development [J/OL]. Science and Technology of Food Industry, 2020: 1-8 [Accessed on September 19, 2020]. https://doi.org/10.13386/j.issn1002-0306.2020050142.

About the Author

Xiaonisha, a food technology professional holding a Master's degree in Food Science, is currently employed at a prominent domestic pharmaceutical research and development company. Her primary focus lies in the development and research of nutritional foods, where she contributes her expertise and passion to create innovative products.