induced Osteoporosis (GIOP) is a metabolic bone disease characterized by decreased bone strength and increased fracture risk due to endogenous or exogenous glucocorticoids, and is the most common form of secondary osteoporosis, with the third highest incidence of all osteoporosis after postmenopausal osteoporosis and senile osteoporosis.
Several studies have shown that bone loss begins after a few weeks of glucocorticoid treatment, and bone loss is rapid within the first few months, up to 5%-15% per year, while the incidence of osteoporosis in patients receiving long-term GC therapy (more than 1 year) can be 30%-50%. Meanwhile, the incidence of glucocorticoid osteonecrosis of the femoral head (SANFH) is increasing year by year with the application of a large number of hormones in the clinic, and SANFH is irreversible once it appears and has a very high disability rate. Therefore, the effective prevention and treatment of GIOP is an important problem that needs to be solved in modern medicine. Li Wei, Department of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
I. Pathogenesis of GIOP
The pathogenesis of GIOP has the following aspects.
① Direct damage to osteoblast, osteoclast and osteoclast functions, reduced bone formation and increased bone resorption; however, unlike general osteoporosis, GIOP is dominated by defects in bone formation.
(ii) Decreased bone reconstruction function, decreased repair ability after bone micro-injury, increased bone fragility, and susceptibility to fracture and osteonecrosis.
(iii) Excessive secretion of PTH causes secondary hyperparathyroidism.
④GC antagonizes gonadal function directly or through indirect pathways, inhibiting the bone-forming effects of gonadotropins, GH and IGF-1.
⑤GC causes muscle atrophy and muscle weakness, and stress load on bones is reduced.
(6) Intestinal absorption and renal tubular reabsorption of calcium are reduced, and negative calcium balance promotes further development of secondary hyperparathyroidism.
II. Risk factors for GIOP
Bone loss occurs regardless of who is applying high doses of glucocorticoids (prednisone dosage of 10 mg/d or more); both natural and synthetic glucocorticoids can cause GIOP. risk factors for GIOP are different from general osteoporosis and have the following significant features.
① Elderly and postmenopausal ;
②The duration of use is longer than 3 months;
③Family history of osteoporosis;
④Low calcium diet and vitamin D deficiency. The effect of glucocorticoids on bone is dose- and time-dependent. At the same BMD, the risk of fracture is significantly higher in GIOP than in postmenopausal osteoporosis.
III. Clinical presentation characteristics of GIOP.
Although GIOP can cause serious consequences, its early symptoms are relatively insidious, and most patients only show symptoms such as back pain, weakness and limb twitching, which are not given sufficient attention, and only in severe cases do skeletal pain occur, and even fractures of the spine, ribs, hip or long bones occur after minor injuries, when severe osteoporosis has developed. Osteonecrosis is an important feature of GIOP, and the common site is the femoral neck. Early CT of osteonecrosis shows disorganization of trabecular structures in the necrotic area, loss of stellate trabecular structures in the femoral head, with dotted hyperdense shadows and osteoporotic changes in the surrounding normal osteophytes.
Glucocorticoid-induced fractures have three characteristics: first, the risk of fracture is independent of age, sex and underlying disease; second, hip fractures and rib fractures can still occur even when BMD is normal, thus there seems to be no safe dose of glucocorticoids that cause bone loss and fractures; third, muscle weakness and myopathy reduce balance and predispose to falls and fractures.
IV. Diagnostic points of GIOP
GIOP can be diagnosed if there is a history of long-term use of glucocorticoids, and if there is a fragility fracture caused by glucocorticoids, the main diagnostic indexes include bone biochemical measurement, bone morphological examination and BMD measurement. The method of BMD measurement and diagnostic criteria are the same as those for primary osteoporosis. It should be noted that the fracture threshold for GIOP is significantly lower than that for other causes of osteoporosis. Vertebral or hip fractures can occur when the T value is below -1.5.
V. Prevention and treatment of GIOP
1.General measures
First, reduce the dose of GC use and shorten the course of treatment as much as possible. Since any dose of GC will accelerate bone
loss and increase the risk of fracture, the new 2010 edition of the American College of Rheumatology (ACR) GIOP guidelines recommend that patients at any dose and with an expected duration of therapy longer than 3 months need to be counseled and evaluated regarding lifestyle when starting GC therapy. “It is never too early to start treatment for GIOP, and (even if an early intervention is missed,) it is never too late to start at any time.”
The prevention component for patients using GC was increased from five items in the old version (smoking cessation, alcohol cessation, weight-bearing exercise, calcium and vitamin D supplementation, and BMD testing) to 17 items. Smoking cessation and limiting alcohol consumption to avoid falls were recommended. All patients starting GC therapy should be supplemented with calcium and vitamin D. Recommended dose of calcium: diet + supplementation 1200-1500 mg/d; vitamin D supplementation to achieve therapeutic levels of serum 25(OH)D3 or a target dose of 800-1000 U/d; moderate levels of vitamin D are necessary for the body, and the minimum serum 25(OH)D3 level should be >50 nmol/L. Vitamin D should be supplemented throughout the treatment at a dose of at least 800 U/d, because GC can impede the absorption of vitamin D. Together with the fact that some people applying GC cannot walk around frequently due to their heavy condition, the amount of vitamin D required may be greater.
2. Assessment of fracture risk
GIOP fragility fractures occur as a result of multiple factors, including decreased BMD, falls and underlying risk. There are a number of flaws and drawbacks in determining fracture risk based on BMD alone. there is a significant negative correlation between GC cumulative dose and bone mineral density (BMD), i.e. the higher the GC cumulative dose, the lower the BMD, but the correlation between GC cumulative dose and fracture risk is not strong.
Therefore BMD is not used as a risk factor to predict the risk of fracture in GIOP, unlike other types of osteoporosis. The new ACR guidelines for GIOP, which are graded according to low (<10%), moderate (10%-20%), and severe (>20%) fracture risk, not only guide the selection of treatment strategies and medications, but also improve patient compliance with treatment. The GIOP guidelines released by the International Osteoporosis Foundation (IOF) in 2012 suggested that the dose and duration of glucocorticoid use were not considered in FRAX, which calculates the 10-year fracture risk at 2.5-7.5 mg/d, and the results may be underestimated or overestimated for patients with high and low doses.
3. Therapeutic drugs
The new edition of the guidelines recommends four drugs for the prevention and treatment of GIOP: alendronate, risedronate, zoledronic acid, and teriparatide. Some data suggest that other drugs such as ibandronate, hydroxydronate, calcitonin, estrogens, androgens, and raloxifene may be effective, but they are not recommended due to lack of support from large samples and high-quality literature. The new version of the guidelines provides a framework model map for the prevention and treatment of GIOP in two populations: postmenopausal women and men over 50 years of age and premenopausal women and men under 50 years of age.
It is not only based on the size of the T-score scores . Rather, the decision of dosing was based on low, moderate, and severe fracture risk (clinical assessment or FRAX calculation) and incorporated factors such as GC dose (0, 5, 7.5 mg) and duration of therapy (<1, 1 to 3, >3 months).
Sixth, Chinese medicine to prevent and treat glucocorticoid osteoporosis
According to the theory of Chinese medicine, “the kidneys store essence” and “the kidneys are responsible for bone and marrow production”. Glucocorticoids are exogenous “pure yang” products – masculine, warm and dry, which act on the human body for a long time, depleting the kidney essence, depriving the bone marrow of its biochemical source, making the bone impotent and weak due to loss of moistening, and causing Osteoporosis. In the long run, kidney deficiency and spleen deficiency will lead to deficiency of spleen and spleen energy, which will lead to stagnation of blood and lack of distribution of essence, which will lead to deficiency of essence and reduction of bone dryness and aggravate the formed osteoporosis.
Therefore, glucocorticoid osteoporosis is a drug-derived bone disease, and its location is in the bone. Kidney deficiency and marrow deficiency are the main pathological mechanisms of glucocorticoid osteoporosis, which is also related to spleen deficiency and blood stasis. Therefore, Chinese medicine treatment is mainly based on tonifying the kidney and strengthening the bone and marrow, as well as strengthening the spleen and invigorating the blood.