Osteoporosis, four major types of drugs, how to step up and personalize the use of drugs?

Osteoporosis (OP) is one of the most common age-related bone diseases in clinical practice, which is characterized by decreased bone mass, damage to bone tissue microstructures, increased bone fragility, and easy fractures, and is a systemic metabolic bone disease that can occur at any age. Pain, spinal deformation, and fragility fractures are the most typical clinical manifestations of OP, which can be divided into primary and secondary OP.

At present, the main anti-OP drugs are:

Calcium and vitamin D and other basic therapeutic drugs,

Bisphosphonates, estrogens, selective estrogen receptor modulators (SERMs, raloxifene, etc.), calcitonins, RANKL inhibitors (desulumab, etc.) and other bone resorption inhibitors,

bone formation promoters parathyroid hormone analogues (PTHa, tripaptide, etc.),

Dual-mechanism drugs, such as active vitamin D and its analogues (α-calcinol, calcitriol, etc.), strontium salt drugs, vitamin K2 drugs, etc.

First, stepwise medication

Anti-OP drugs usually prefer drugs with a broad anti-fracture spectrum (bisphosphonates such as alendronate, zoledronic acid, riscedronic acid, and the RANKL inhibitor destrumab).

The Guidelines for the Diagnosis and Treatment of Primary Osteoporosis (2017) indicate that oral medication is preferred in patients at low and moderate fracture risk (e.g., young postmenopausal women, patients with low bone density levels but no history of fractures). Injectable agents (eg, zoledronic acid, PTHa teripate, desuzumab, etc.) may be considered in patients with oral intolerance, contraindications, and a high risk of fractures (e.g., elderly patients with multiple vertebral or hip fractures, and very low bone density). If there is only a high risk of vertebral fractures, and the risk of hip and non-vertebral fractures is not high, estrogens or SERMs may be considered.

According to the Expert Consensus on the Diagnosis and Treatment of Osteoporotic Vertebral Compression Fractures (2021 Edition), the American Association of Endocrinologists (AACE) and the American Endocrine Association (ACE) 2020 Postmenopausal Osteoporosis Diagnosis and Treatment Guidelines define osteoporosis patients who have fractured and fractured multiple fractures in the past 12 months as extremely high fracture risk, recommending injectable dosage forms such as zoledronic acid, desulumab, and teripab as initial treatment; for those with high fracture risk, sodium alendronate, desulzumab, and licedrinate sodium are recommended. Zoledronic acid as the initial treatment.

The "Clinical Practice Guidelines for the Drug Treatment of Endoopausal Osteoporosis in Postmenopausal Women" (2019) points out that postmenopausal women with a high risk of fracture can choose bisphosphonates, desuzumab or tripatinide for initial treatment, and SERMs and calcitonin drugs can also be used when the above cannot be tolerated or obtained.

In the Identification and Prevention Strategies of Patients with High Fracture Risk of Osteoporosis (2020), it is pointed out that when treating patients with very high fracture risk or multiple fractures, bone formation promoters such as PTHa are preferred compared with bone resorption inhibitors, because their effect on reducing fracture risk is stronger and more effective; for patients with high fracture risk, bisphosphonate drugs are recommended as the initial treatment choice; and desultimab is recommended as an alternative initial treatment option for postmenopausal women with high fracture risk.

The "2020 Edition of China's Expert Consensus on the Prevention and Treatment of Glucocorticoid Osteoporosis" pointed out that the initial treatment of patients with glucocorticoid osteoporosis (GIOP) with medium and high fracture risk, in addition to calcium and (active) vitamin D, oral or intravenous bisphosphonate drugs are preferred; if bisphosphonate drugs are intolerable, teriparaben, and raloxifen (limited to postmenopausal women) can be selected.

For postmenopausal female OP with high fracture risk, MALE OP with high fracture risk, GIOP in men and women with high fracture risk, men with high fracture risk who have high fracture risk, men with high fracture risk non-metastatic prostate cancer who receive androgen deprivation therapy, and women with high fracture risk of breast cancer receiving aromatase inhibitor therapy, desulumab therapy is recommended to increase bone mass.

Bone formation promoters are recommended for women over 65 years of age with osteoporotic vertebral fractures with bone density below -2.5 SD, multiple osteoporotic vertebral fractures or hip fractures in postmenopausal women, osteoporosis fractures that occur after use of bisphosphonates, and PTHa is recommended for multiple fractures of osteoporosis after menopause or severe POSTmenopausal OP, bisphosphonate treatment, severe osteoporosis fractures (T-value <-3.0) or multiple osteoporosis fractures.

SERMs are recommended for those with a high risk of fracture and a low risk of DVT, no use of bisphosphonates or disuzumab, or breast cancer, and postmenopausal hormone replacement therapy may be considered for people under 60 years of age or within 10 years of menopause who are at high risk of fracture or who do not use bisphosphonates or desulizumab and are not at risk of breast cancer. For patients with perimenopausal osteoporotic fractures, estrogens are available when menopausal symptoms (vasomotor symptoms) are apparent, and SERMs are available if there are no significant menopausal symptoms.

Second, personalized medication

Bone resorption inhibitors are used for OP caused by active bone resorption function of osteoclasts. Bone formation promoters are used for OP caused by decreased osteoblast activity.

Elderly OP (i.e., osteoporosis type II), it is recommended that elderly OP or elderly people with low bone mass with a high risk of fracture be based on calcium and /or vitamin D in combination with antiOP drugs. Among them, bisphosphonate drugs can be used for elderly OP; SERMs can be used for op in elderly women; PTHa can be used for elderly OP with high risk of vertebral or non-vertebral fractures and poor efficacy, contraindications or intolerance to bone resorption inhibitors, or elderly or severe OP with very high risk of vertebral or non-vertebral fractures; vitamin K2 drugs are suitable for elderly OP with low fracture risk or renal insufficiency.

The acceleration of bone loss after menopause is related to estrogen deficiency, and the treatment drugs for postmenopausal OP (that is, type I osteoporosis) are mainly sex hormone drugs, bisphosphonate drugs, SERMs, desulumab, teriparaben, calcitonin drugs, etc. The Expert Consensus on osteoporosis prevention and treatment in perimenopausal and postmenopausal women (2020) states that hormone therapy (HT) is a first-level preventive measure for postmenopausal osteoporosis.

Male OP treatment drugs include bisphosphonate alendronate, zoledronic acid, riscedronic acid, calcitonin drugs, active vitamin D and its analogues, desulumab, and teripate.

Low bone conversion OP, more common in elderly OP patients, its treatment should be preferred bone formation promoter to improve bone microstructure, promote bone mass formation, reduce the risk of re-fracture; high bone conversion OP, more common in postmenopausal women, postmenopausal OP bone resorption is rapid, bone metabolism conversion rate is high, bone resorption inhibitors can be selected.

Osteoporotic fracture perioperative patients general pain symptoms are obvious, bone resorption enhancement, bed rest and immobilization will lead to accelerated bone loss, it is advisable to choose bone resorption inhibitors, although it affects the remodeling of the scab, but does not affect the recovery of fracture mechanical integrity, such as zoledronic acid, disolemab, etc. do not affect fracture healing, bisphosphonate drugs can also reduce internal fixation or bone loss around the prosthesis, improve the stability of hip bone mass and internal fixation, reduce the incidence of internal fixation or displacement and the incidence of prosthesis release, Improve the efficacy of surgery.

For OP patients with moderate to severe bone pain or perioperative fractures, calcitonins are recommended to relieve osteoporosis bone pain and also prevent acute bone loss. In addition, short-term use may be considered in patients with new fractures with pain.

PTHa can not only promote the healing of vertebral fractures, significantly shorten the healing time of fractures, but also promote the formation of scabs, improve the bone mass and bone quality of the vertebral body, improve the biomechanical properties of bones, improve the degree of mineralization of scabs, reduce the incidence of loose screws in the vertebral pedicle, and improve the efficacy of surgery.

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