Peptides for Osteoporosis Research

Introduction to Osteoporosis

Osteoporosis is a systemic multi-causal skeletal disease that is prone to fractures due to changes in systemic bone mass and microstructure of bone tissue, resulting in increased bone fragility. Osteoporosis is a type of disease that is difficult to cure. According to the etiology, it can be divided into primary osteoporosis, secondary osteoporosis and idiopathic osteoporosis. Primary osteoporosis, including postmenopausal osteoporosis and senile osteoporosis. Postmenopausal osteoporosis, also known as type I osteoporosis, typically occurs within 5-10 years after menopause in women and is associated with postmenopausal estrogen insufficiency. Senile osteoporosis, also known as type II osteoporosis, generally refers to osteoporosis that occurs after the age of 70, and is related to changes in aging. Secondary osteoporosis is osteoporosis that exists as a secondary symptom of certain diseases. The etiology is an established disease or other factors, including endocrine disease, connective tissue disease, bone marrow disease, drug factors, nutritional factors or disuse factors. Idiopathic osteoporosis is defined as osteoporosis that is not caused by any currently known cause. Idiopathic osteoporosis includes idiopathic juvenile osteoporosis and idiopathic adult osteoporosis. The main diagnosis of idiopathic osteoporosis is that the bone mass at the onset is significantly lower than that of the age.

Current Status of Osteoporosis

Osteoporosis has now become a global public health problem. The consequences are far worse than people imagined. Twenty percent of older adults die within a year of a fracture, and 50 percent have since lost their ability to live independently. In European countries such as the United States and the United Kingdom, the incidence of osteoporosis accounts for about 60% of the elderly population. Middle-aged people suffering from osteoporosis disease is not a minority. Data show that nearly 30 percent of men between the ages of 35 and 50 suffer from osteopenia, a sign of weakened bones and a precursor to osteoporosis. According to the statistics of American medical experts, about 10 million Americans suffer from osteoporosis, and another 34 million people have low bone density. About 2 million fractures occur each year due to osteoporosis, 70% of which are women. Even more surprising is that the number of Americans suffering from osteoporosis has increased by more than 6 times in 10 years, according to the findings released by researchers at Stanford University.

Clinical Manifestations of Osteoporosis

The clinical manifestations of osteoporosis mainly include the following three categories of symptoms:

(1) Pain

Chronic low back pain of unknown origin is the most common symptom in patients with osteoporosis. Patients often experience low back pain, extensive bone and joint pain, or general soreness when turning over, sitting up, and after walking for a long time. When the load increases, the pain increases and even the movement is limited.

(2) Spinal deformity

Patients with severe osteoporosis may have spinal deformities such as shortened height and hunched back. Spinal deformities can aggravate spine and lower extremity joint pain. Vertebral compression fractures can cause thoracic deformity, abdominal compression, and affect cardiopulmonary function.

(3) fragility fractures

Fractures that occur non-traumatically or with minor trauma are fragility fractures, such as falls from or below standing height or from other everyday activities. A fragility fracture is the ultimate manifestation of decreased bone strength. Hip and vertebral fragility fractures are important clinical manifestations of osteoporosis.

Causes of Osteoporosis

The etiology and pathogenesis of osteoporosis are complex. Risk factors for osteoporosis include aging, gender and ethnicity, family history, low calcium and high protein diet, medications (eg, corticosteroids and anticonvulsants), smoking, excessive alcohol consumption, lack of exercise, endocrine factors (estrogen deficiency), androgen reduction, calcitonin deficiency), other diseases (such as intestinal problems, kidney problems, liver disease). Generally speaking, it is the abnormality of hormone regulation, nutritional factors, physical factors, genetic factors, immune function, etc., as well as some drug factors.

Treatment of Osteoporosis

So far there is no effective treatment to rebuild the already loose bone. Therefore, early measures for prevention and effective treatment have attracted more and more attention. At present, the clinical anti-osteoporosis drugs are mainly divided into two categories. One is a drug that inhibits bone resorption, and the other is a drug that promotes bone formation.

• Drugs That Inhibit Bone Resorption

(1) Bisphosphonates

Bisphosphonates are the mainstream drugs for the prevention and treatment of osteoporosis. It inhibits the synthesis pathway of cholesterol in osteoclasts, promotes the early apoptosis of osteoclasts, and inhibits the migration and attachment of osteoclasts. Currently, the bisphosphonates approved for the prevention and treatment of osteoporosis are alendronate, risedronate, ibandronate, and zoledronate.

(2) Calcitonins

Calcitonin is a short peptide consisting of 32 amino acids secreted by parafollicular cells of the thyroid. Calcitonins are more suitable for osteoporosis patients with painful symptoms.

(3) Denosumab

Denosumab is a RANKL monoclonal antibody drug. Denosumab inhibits bone resorption and reduces the risk of fractures and has been approved for the treatment of postmenopausal osteoporosis and osteoporosis in men.

(4) Selective Estrogen Receptor Modulators

Selective estrogen receptor modulators, which act as estrogen-like and estrogen-like antagonists, reduce the risk of invasive breast cancer in postmenopausal women with osteoporosis and women at high risk for invasive breast cancer.

(5) Estrogen

Estrogens are suitable for women with menopausal symptoms (such as hot flashes, sweating, etc.) and/or osteoporosis and/or risk factors for osteoporosis. Hormone therapy also carries potential risks, such as a possible increased risk of cardiovascular events, breast cancer, deep vein thrombosis, pulmonary embolism, and gallbladder disease.

• Drugs That Promote Bone Formation

(1) Parathyroid Hormone

Parathyroid hormone (PTH) as a bone formation promoter can effectively promote bone reconstruction, increase bone density, and prevent fractures.

 (2) Parathyroid Hormone-Related Protein Analogs

Parathyroid hormone-related protein (PTHrP) has high homology with PTH, and can effectively promote bone synthesis in both experimental animals and humans.

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