primary immunoglobulin light chain amyloidosis ( al amyloidosis ) is a plasma cell disorder which mainly affects heart , kidneys , liver , and peripheral nervous system . cases of atypical al amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported , and data about the management and clinical outcomes of the patients are scarce . herein , we present 3 new cases of al amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature . moreover , we observed overrepresentations of liver involvement and bone marrow involvement in al amyloidosis with spontaneous vertebral compression fracture . we believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of al amyloidosis can facilitate earlier diagnosis and earlier treatment . primary immunoglobulin light chain amyloidosis ( al amyloidosis ) is a plasma cell disorder characterized by overproduction and accumulation of insoluble amyloid fibrils composed of immunoglobulin light chains . the most commonly affected organs are the heart , kidneys , liver , and peripheral nervous system , presenting as congestive cardiomyopathy , nephrotic - range proteinuria , hepatomegaly , and peripheral neuropathy , respectively . a spontaneous vertebral compression fracture is a rare clinical presentation in patients with al amyloidosis . here we present 3 cases of al amyloidosis with spontaneous vertebral compression fractures , liver involvement , and bone marrow involvement , with a review of the literature . all patients provided signed , informed consent , and the study was approved by peking union medical college hospital institutional review broad . case 1 was a 64-year - old man who had his thoracic spine fractured accidentally 5 years ago . a computed tomography scan was performed and suggested a vertebral compression fracture of t11 . he had a spontaneous lumbar compression fracture of l1 to l2 6 months later . another 6 months later , he developed soy urine . an abdominal ultrasound showed that the liver edge was near the costal margin and 3.7  cm below the xiphoid process . the laboratory tests revealed the following : hemoglobin , 143  g / l ( normal , 120160 g / l ) ; gamma - glutamyl transpeptidase ( ggt ) , 656  u / l ( normal , 1060  u / l ) ; alkaline phosphatase ( alp ) , 477  u / l ( normal , 50135 u / l ) ; albumin , 34  g / l ( normal , 3552  u / l ) ; creatinine , 89  mol / l ( normal , 59104  mol / l ) ; 24-hour urine protein , 5.87  g ( normal , 0.000.20  g ) ; serum phosphate , 1.45  mmol / l ( normal , 0.811.45  mmol / l ) ; calcium , 2.17  mmol / l ( normal , 2.132.70  mmol / l ) ; serum cardiac troponin i ( ctni ) , 0.02  g / l ( normal , 00.04  g / l ) ; n - terminal of the prohormone brain natriuretic peptide ( nt - probnp ) , 213  pg / ml ( normal , 0125  pg / ml ) ; serum protein electrophoresis ( spep ) , negative monoclonal protein ; serum free light chain ( flc ) kappa , 51.6  mg / dl ; serum flc lambda , 10.5  mg / dl ; serum flc ratio ( flc - r ) , 4.91 ; difference between involved and uninvolved serum immunoglobulin flc ( dflc ) , 40.1  mg / l ; bone marrow biopsy , amyloid deposits with 3.5% plasma cells ; immune staining , predominant kappa light chains ; and liver biopsy , amyloid degeneration with positive congo red staining . he was treated with 6 cycles of bortezomib , cyclophosphamide , and dexamethasone , and reached hematologic complete remission ( cr ) . at the follow - up examination 2 years later , the organ response was documented with a negative 24-hour urine protein , an alp of 153  u / l , and a ggt of 322 case 2 was a 49-year - old woman who complained of progressive back pain for 5 years and was found to have multiple spontaneous vertebral fractures . magnetic resonance imaging revealed old compression fractures involving t11 to t12 and l1 to l4 . the physical examination was notable for macroglossia and liver enlargement with a liver edge palpable 6  cm below the costal margin and 4  cm below the xiphoid process . laboratory tests indicated the following : hemoglobin , 117  g / l ( normal , 110150 g / l ; creatinine , 72  mol / l ( normal , 4584  mol / l ) ; alp , 165  u / l ; ggt , 261  u / l ; nt - probnp , 309  pg / ml ; ctni , 0.00  g / l ; serum calcium , 2.30  mmol / l ; serum phosphate , 1.4  mmol / l ; serum parathyroid hormone , 31.7  pg / ml ( normal , 12.065.0  pg / ml ) ; 24-hour urine protein , 0.41  g ; spep , no monoclonal protein ; serum flc kappa , 43.2 mg / l ; dflc , 30  mg / l ; flc - r , 3.27 ; and bone marrow ( plasma cells1% ) , gingival , and tongue biopsies , scattered interstitial amyloid deposition with positive congo red stain . the patient was treated with high - dose melphalan ( 200  mg / m ) followed by autologous stem cell transplantation ( asct ) . the alp was 153  u / l , and the ggt was reduced to 80  u / l . case 3 was a 48-year - old man who presented with lower back pain and increasing abdominal girth over the past year . the physical examination revealed hepatomegaly with the liver edge palpable 7  cm below the costal margin and 12  cm below the xiphoid process . a chest x - ray revealed multiple spontaneous vertebral and old costal fractures involving the right third and fourth ribs , as well as the left eighth rib . g / l ; creatinine , 75  mol / l ; alp , 330  u / l ; ggt , 445  u / l ; serum calcium , 2.36  mmol / l ; serum phosphate 1.35  mmol / l ; parathyroid hormone , 14.5  pg / ml ; nt - probnp , 108  pg / ml ; ctni , 0.00  g / l ; 24-hour urine protein , 0.36  g ; spep , monoclonal protein ( 0 g / l ) ; serum flc kappa , 70.6  mg / dl ; serum flc lambda , 10.6  mg / dl ; dflc , 60.0  mg / l ; flc - r , 6.66 ; bone marrow biopsy , 0.50% plasma cells , with amyloid fibrils deposited near vessels ; and liver biopsy , large amount of amorphous amyloid deposits between hepatic cells , which were positive in congo red stain . the patient was treated with melphalan , dexamethasone , and daily thalidomide . during the past 6 months since he completed treatment , he achieved a hematologic cr , with a decrease in ggt ( 233  u / l ) and alp ( 224  u / l ) . the general functional status was largely improved with no additional vertebral fractures . spontaneous vertebral compressions are rare manifestations in patients with al amyloidosis . in our case series , spontaneous vertebral compression fractures were one of the initial presenting signs of al amyloidosis . interestingly , all 3 patients in this case series had liver involvement , as demonstrated by hepatomegaly and elevation in liver enzymes , especially alp and ggt , as well as bone marrow involvement . in addition , none of the 3 patients had severe cardiac problems or involvement of other major organs . we reviewed the literature and found 13 reported patients with al amyloidosis who presented clinically with spontaneous vertebral fractures ; the characteristics of these cases are shown in table 1 . the median age of the 13 patients was 59 years ( range , 2976 years ) . it is worth noting that of 11 reported cases , 8 ( 72.7% ) also had liver involvement , 10 ( 90.9% ) had bone marrow involvement , and 7 ( 63.6% ) had both liver and bone marrow involvement , while only 1 patient had cardiac involvement , which was consistent with organ involvement in our case series . al amyloidosis with presentation of vertebral compression fractures in the literature . in patients with al amyloidosis who presented with vertebral compression fractures , one possible explanation would be the potential kappa light chain dominance among the patients with vertebral bone involvement . according to table 1 , of note , while kappa - predominance was observed in the patients with vertebral fractures and bone marrow involvement , the lambda - to - kappa light chain ratio in patients with al amyloidosis is 3.8 . this is in agreement with a former study indicating that the tropism of organ involvement in al amyloidosis can be influenced by the light chain variable region , which supports the hypothesis that patients with kappa light chains are more likely to have hepatic involvement . in another study , soft tissue and bone involvement was considered , the kappa - to - lambda ratio was 1 , and the major soft tissue and bone involvement included macroglossia and vertebral compression fractures . the mechanism underlying spontaneous vertebral compression fractures in al amyloidosis has not been identified . in most cases with compression vertebral fractures , biopsies indicate nearly complete replacement of the bone marrow by amyloid fibrils . in addition , all patients reported with al amyloidosis presenting with vertebral fractures had normal serum calcium , serum phosphatase , and serum parathyroid hormone levels , which was the same as our 3 cases . a possible explanation is that neither osteolytic lesions nor disorders of calcium phosphate metabolism cause multiple vertebral fractures in patients with al amyloidosis . instead , amyloid fibrils are first deposited near blood vessels supporting vertebrae , which may cause nutritional insufficiency in vertebrae , leading to progressive loss of bone density , and finally contributes to the compression fractures . such a mechanism is different from that in amyloidosis associated with multiple myeloma , where lytic lesions are commonly associated and become the major cause of bone fractures . treatment of the patients in this series was no more special than other cases with al amyloidosis , except that surgery using bone cement was often used in managing vertebral fractures . melphalan , bortezomib , thalidomide , cyclophosphamide , dexamethasone , and asct were used to treat our patients . fortunately , all 3 patients responded well , with an improvement in symptoms and functional status . such a favorable prognosis is largely attributed to the early diagnosis and early treatment of al amyloidosis . during the past few decades , several patients with initial fractures in vertebrae have been reported to have died from al amyloidosis due to delayed diagnosis as well as inappropriate treatment . given our results and the reports in the literature , even though vertebral compression fractures are rare in al amyloidosis , it is still important to consider al amyloidosis in the differential diagnosis of spontaneous vertebral compression fractures , especially in patients with hepatomegaly or elevated liver enzymes . bone marrow biopsy is necessary , since most of the patients can have bone marrow infiltration of amyloid deposits . the functions of major organs are largely normal in most patients ; thus , early diagnosis and early treatment are of great significance for such atypical cases of al amyloidosis .
abstractbackground : primary immunoglobulin light chain amyloidosis ( al amyloidosis ) is a plasma cell disorder which mainly affects heart , kidneys , liver , and peripheral nervous system . 
 cases of atypical al amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported , and data about the management and clinical outcomes of the patients are scarce.methods:herein , we present 3 new cases of al amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature.results:moreover , we observed overrepresentations of liver involvement and bone marrow involvement in al amyloidosis with spontaneous vertebral compression fracture.conclusion:we believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of al amyloidosis can facilitate earlier diagnosis and earlier treatment .