How to prevent osteoporosis with long-term application of "hormones"?

*For medical professionals only, how should this type of osteoporosis be treated? Glucocorticoids (GC) are commonly used anti-inflammatory and immunosuppressive drugs in rheumatology, and long-term use can lead to osteoporosis, namely glucocorticoid-induced osteoporosis (GIOP)
.

GIOP is one of the most common adverse reactions of long-term use of GC, and one of the most common causes of secondary osteoporosis, which is characterized by a persistent decline in bone formation, accompanied by increased bone resorption, leading to an increased incidence of fractures, which can be severe in severe cases.
It can cause fractures of vertebral body, ribs and hip bones, seriously affecting the quality of life of patients
.

Studies have shown that in patients with long-term GC use, fractures occur in up to 40% of patients if osteoporosis treatment is initiated inappropriately
.

A large-scale epidemiological survey in China shows that the incidence of osteopenia and osteoporosis in rheumatism patients receiving GC treatment is as high as 80%.
Even with low-dose GC, there are still 58.
5% of patients with osteoporosis.
About 1/3 of the patients have never received any standardized prevention and treatment
.

When to start and stop osteoporosis drugs in GIOP patients has received a lot of attention, but there is still a lack of clear guideline recommendations
.

Kaleen N et al [1] published a review outlining current guideline recommendations for initiating and discontinuing osteoporosis therapy in patients with GIOP and providing medication recommendations for the use of osteoporosis therapy based on available evidence
.

Uncover the fog and explore the pathogenesis of GIOP.
The main feature of GIOP is the persistent decrease in bone formation with increased bone resorption, which is different from the pathogenesis of postmenopausal osteoporosis
.

GC increases fracture risk through multiple mechanisms, destroying osteoblasts and osteoclasts that build and break down the balance of the bone remodeling cycle, respectively
.

Bone loss caused by GC mainly occurs in two periods.
The first period is a rapid initial phase, with approximately 29% bone loss in the first 6 months of GC use, and the bone density is stabilized at 0.
5%-2% per year.
decline
.

The effect of GC on osteoblasts: Osteoblasts are derived from bone marrow mesenchymal stem cells, and their main role is to promote bone formation
.

Osteoblasts also secrete a variety of bone matrix proteins, such as type I collagen, osteocalcin, etc.
, which are involved in bone anabolism and micro-damage repair
.

GC can reduce osteoblast differentiation and maturation and inhibit bone formation
.

The effect of GC on osteoclasts: Osteoclasts account for 1%-2% of skeletal cells and are differentiated from monocyte-macrophage precursors
.

GC promotes bone resorption by promoting osteoclast differentiation and maturation and prolonging the lifespan of osteoclasts
.

The effect of GC on osteocytes: Osteocytes secrete collagen type I, sclerostin, DKK-1 and other substances, and play an important role in integrating signals, regulating bone remodeling, and regulating the activity of osteoblasts and osteoclasts
.

Compared with the general population, patients using GC can have fractures at higher bone density, suggesting that in addition to bone density, GC damages bone strength more significantly, which is also closely related to the impairment of bone cell function
.

Follow the vine and grasp the timing of starting and stopping osteoporosis treatment ■ When should osteoporosis treatment start? GC can lead to fracture through various mechanisms, such as prolonging the lifespan of osteoclasts and affecting the apoptosis of osteoclasts
.

At the same time, a meta-analysis showed that, regardless of the daily dose, bone mineral density decreased rapidly in the first three months of treatment with GC
.

In general, regardless of age or GC dosage, all patients who have received GC therapy for ≥3 months and have a history of fractures should start osteoporosis therapy
.

For patients without a history of fractures, a fracture risk assessment (FRAX score) is recommended, taking into account clinical risk factors (eg, age, gender, GC dose) to determine the need for treatment
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However, treatment thresholds differ between guidelines, possibly due to the lack of evidence to validate that the anti-osteoporotic benefit of GIOP treatment differs in patients with different fracture risk factors
.

Study [2] found that even after 6-12 months of high-dose GC therapy, fracture risk and bone loss rates appeared to start to stabilize
.

 Table 1: Fracture Risk Stratification ■ When should osteoporosis treatment be stopped? It is generally accepted that GIOP is reversible to some extent
.

Preclinical studies have shown that this reversibility is associated with a rapid recovery of osteoblasts after GC discontinuation
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Therefore, typically, osteoporosis treatment is discontinued after GC is discontinued
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According to the "2020 Chinese Expert Consensus on the Prevention and Treatment of Glucocorticoid GC Osteoporosis" [3], only those who discontinue GC therapy and whose fracture risk is reassessed as low risk can discontinue osteoporosis drugs
.

Calcium and vitamin D should be supplemented after discontinuation, and fracture risk should be assessed every 12 months
.

An earlier study of intermittent use of GC showed that fracture risk returned to baseline in patients with cumulative total GC <1 g after 6 months, whereas fracture risk did not decrease to baseline in patients with GC ≥ 1 g until 15 months later
.

In contrast, a Danish RCT study found no significant reduction in the risk of spinal fractures 1 year after GC discontinuation
.

At present, there are no guidelines at home and abroad that clearly recommend the specific time for stopping osteoporosis treatment
.

In conclusion, when to stop osteoporosis treatment after GC is stopped, more verification is needed
.

How to choose osteoporosis treatment? Despite the general belief that patients at risk of fracture should be started on osteoporosis medications, current GIOP guidelines are inconsistent in their approach to treatment
.

Only the 2017 ACR guidelines [4] explicitly recommend oral bisphosphonates (in addition to calcium and vitamin D supplementation) therapy
.

Guidelines from the International Osteoporosis Foundation and the European Society for Calcified Tissues (IOF-ECTs) [5] and the UK National Osteoporosis Guidelines Group (NOGG) [6] recommend considering oral bisphosphonates as first-line therapy in patients with GIOP
.

Oral bisphosphonates have been shown in the ACR guidelines to be the preferred first-line therapy for the prevention of GIOP fractures due to their high efficacy, low cost, and favorable safety profile in patients with immunosuppressive agents
.

For patients who are ineffective or intolerant of oral bisphosphonates, the guidelines recommend zoledronic acid and denosumab as second-line therapy
.

According to the "2020 Edition of Chinese Expert Consensus on the Prevention and Treatment of Glucocorticoid-induced Osteoporosis" [3], in the initial treatment of GIOP, those with low fracture risk are recommended to adjust their life>
etc.

SUMMARY In short, patients undergoing long-term GC therapy should be assessed for fracture risk (FRAX score) and, as appropriate, initiate osteoporosis therapy to prevent GIOP
.

Most guidelines recommend the immediate initiation of osteoporosis therapy in patients receiving high-dose GC, with a history of fracture, or at high risk of fracture
.

At present, there are no guidelines at home and abroad that clearly recommend the specific time for stopping osteoporosis treatment
.

In conclusion, more validation is needed regarding the timing of cessation of osteoporosis treatment after discontinuation of GC
.

 Reference [1] Hayes KN, Baschant U, Hauser B, et al.
When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis[J].
Front Endocrinol (Lausanne), 2021,12:782118.
DOI: 10.
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[2]van Staa TP, Leufkens HG, Cooper C.
The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis[J].
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[3]2020 edition of Chinese expert consensus on the prevention and treatment of glucocorticoid-induced osteoporosis[J].
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[4]Buckley L, Guyatt G, Fink HA, et al.
2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis[J].
Arthritis Rheumatol, 2017,69(8):1521-1537.
DOI:10.
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[5 ]Lekamwasam S, Adachi JD, Agnusdei D, et al.
A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis[J].
Osteoporos Int, 2012,23(9):2257-2276.
DOI:10.
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[6]Compston J, Cooper A, Cooper C, et al.
UK clinical guideline for the prevention and treatment of osteoporosis[J].
Arch Osteoporos, 2017,12(1):43.
DOI:10.
1007/s11657-017-0324-5.