Main clinical manifestations and diagnosis 1. Osteoporosis (Osteoporosis) Osteoporosis is the most common skeletal muscle lesion after organ transplantation, resulting in reduced bone density, bone and joint lesions and fractures. The prevalence of osteoporosis is approximately 28%-73%, with no difference between men and women; the incidence of fractures ranges from 17% to 65%. Clinical manifestations of osteoarthralgia, back pain and fractures are more frequent but later. More than 25% of osteoporosis can be diagnosed by X-ray, but a better method is to do bone mineral density (BMD), which can be diagnosed early, when BMD is below normal 2.5 SDs. The measurement range is better for the lumbar spine and femoral neck. 2, osteonecrosis (Osteonecrosis) This disease is manifested as ischemic necrosis of bone and/or bone marrow (nontraumatic ischemic necrosis). The most commonly affected site is the hip bone, and if not diagnosed in time, the resulting 5-year survival rate decreases from 90% to 15%. Pain is the earliest and most common symptom and is present in the majority of patients, but signs are absent. X-radiology remains negative for several months prior to osteonecrosis. The most typical x-ray presentation is the crescentic sign at the site of osteonecrosis. Nuclear magnetic resonance imaging (MRI) can detect early changes. MRI has been reported to be more than 90% sensitive for osteonecrosis. t1 shows hypointense segmentation lines between normal and ischemic bone tissue; t2 shows parallel high-density lines secondary to dense vascular masses. The Association for Research in Osteocirculation (ARCO) classifies the disease into 5 stages: Stage 0: all diagnostic tests are normal and the diagnosis is made by histology alone. Stage I: Positive MRI and histology. Stage II: positive CT and MRI, negative X-radiology. Stage III: crescentic sign with flattening of the femoral head. Stage IV: arthrosis (joint lesion). 3. Calcineurin inhibitor-induced pain syndrome (CIPS) CIPS usually occurs between 3 and 14 months after transplantation and presents with symmetrical pain in both feet, sometimes radiating to the ankle and knee. The pain is characterized by severe deep burning-like pain that is aggravated by walking or weight bearing. Most patients have to use crutches or wheelchairs. Symptoms may be relieved with a little rest, especially with elevation of the leg. Clinical and radiological examination of the foot was unremarkable in most patients, except for mild osteoporosis. Serum cyclosporine levels were higher than normal in all patients. In stage III patients, microscopic scintigraphy (Scintigraphies) at 1 min, 10 min and 3 h after injection of tracer (e.g. DPD99m) showed characteristic concentrations in the foot joints and bone, suggesting hyperperfusion, hypervascularity and hypermetabolism. MRI shows edema of the anterior tibial joints (talotibial jiont) and soft tissues, and diffuse bone marrow edema in the painful areas of the pedal bone tissue. Reflex sympathetic dystrophy, Avascular necrosis, Polyneurophathy, Atherosclerosis, Morton’s neuralgia should be excluded. Basic tests 1. Biochemical indicators representing bone formation Bone specific alkaline phosphate (B-ALP); Type I procollagen carboxyterminal propeptide (PICP); Type I procollagen aminoterminal propeptide (PICP); Type I procollagen aminoterminal propeptide (PICP); Type I procollagen aminoterminal propeptide (PICP); Type I procollagen aminoterminal propeptide (PICP) (Type I procollagen aminoterminal propeptide, PINP); Osteocalcin; 2, biochemical indicators representing bone resorption: serum type I collagen carboxyterminal telopeptide (ICTP); urinary Imaging: (1) X-ray, (2) CT, (3) MRI, (4) Dual-energy X-ray absorptiometry (DXA): expressed in g /cm2 expression and then converted to T and Z scores. t score is the patient’s bone mineral density (BMD) compared to a normal person of the same sex aged 25-29 years; Z score is the patient’s BMD compared to the overall population expectation of the same age and sex. The overall Z-score is zero for any age, gender and scan location. Definition 2. 5% of the population measured had a Z-score below -2 standard deviations. According to the World Health Organization (WHO) criteria, if the T-score is below -2.5, osteoporosis is diagnosed, and a T-score of -1 to -2.5 is considered as reduced bone mineral density. (5) Isotope testing: the most commonly used is technetium 99 (99m Tc). It allows a bone scan of the whole body and to understand the location of the lesion. It is of little use in the diagnosis of uncomplicated osteoporosis, but is more relevant for the diagnosis of cone fractures caused by osteoporosis. It is characterized by linearly increasing areas of tracer concentration seen at the site of involvement. A positive bone scan can be obtained immediately after the fracture, and the different densities can be used to determine the time of onset of the lesion, which is particularly suitable for the elderly. Prevention and treatment (a) Prevention 1. Reduce bed rest and encourage patients to do more moderate weight-bearing exercises to reduce bone demineralization. Azathioprine is usually used in combination with CSA and corticosteroids. Studies in rats have not found an effect of Azathioprine on bone volume, but it was found to increase the number of osteoclasts; Mycophenolate mofetil (MMF) is a noncompetitive inhibitor of free monophosphate dehydrogenase ( a noncompetitive inhibitor of inosine monophosphate dehydrogenase), which could be used as an alternative to Azathioprine as the primary immunosuppressive agent. Rapamycin is a new T-cell inerting agent (inactivator) and has no evidence of bone loss, but may increase bone repair (remodeling) as well as reduce longtitudinal growth. (ii) Treatment 1. Phosphates, non-nitrogenous bisphosphonates and amino bisphosphonates. The main mechanism of action is to bind tightly with bone trabeculae and form high concentrations of free bisphosphate aggregates on the damaged bone surface to repair the damaged bone; to inhibit the transformation of osteoclast precursor cells into mature osteoclasts and promote the apoptosis of osteoclasts so that they lose their function and reduce bone resorption; to inhibit the synthesis and release of osteoclast pain-causing mediators and inflammatory mediators to relieve clinical symptoms. inflammatory mediators, relieving clinical symptoms. As a preventive measure, if only BMD is reduced without osteoporosis, bisphosphonates are recommended to be given after HSCT and every 3 months thereafter; if osteoporosis or BMD is below normal 2SD, continuous monthly treatment is required. 2. Hormone replacement therapy (HRT): After the application of immunosuppressants in menopausal women, hormone replacement therapy should be considered to reduce osteoporosis and the resulting fracture occurrence. However, long-term HRT should be alert to the occurrence of hormone-related tumors. 3.Other drugs: Calcitriol, Calcitonin, Parathyroid Hormone, and Fluoride can be used as adjuvant therapy. 4.Surgical treatment: surgical excision of necrotic bone lesions. The research on bone metabolism disorder after hematopoietic stem cell transplantation is a new topic for clinical medical workers, and more and more in-depth work is needed.