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in alzahra university hospital of isfahan , iran , the a 42-year - old homemaker woman , who used to suffer from rheumatoid arthritis since 2004 was admitted . during this time
, rheumatoid factor and anti - cyclic citrollinated peptide ( anti - ccp ) always had been negative . in this period , she had wrists , shoulders , knees , and ankles involvement , and never been improved completely .
the patient was under the treatment of oral methotrexate ( 10 mg per week ) , sulfasalazine ( 1500 mg / day ) , diclofenac ( 50 mg / day ) , and low dose prednisolone ( 7.5 mg / day ) .
dose escalation did not improve disease activity score of 28 joints ( das28 > 5.1 ) and laboratory parameters .
she was admitted to the hospital due to refractory joints pain , tenderness , leukocytosis ( 12  10/ul ) , and elevated esr ( 65 mm / h ) and crp ( 42 mg / l ) .
in addition , she received steroid pulses ( iv methylprednisolone sodium succinate 500 milligram ) during each admission .
she was the candidate for biologic therapy , but she could not afford it . due to this problem
after four weeks , she felt better , and ten - derness decreased , but swelling continued .
esr ( 35 mm / h ) and crp ( 22 mg / l ) improved slightly ; but during this period , blood pressure and serum creatinine increased .
unfortunately , by tapering the drug dosage , the clinical and laboratory signs recurred . in respect of anti - inflammatory effect of pamidronate , after signing the inform consent by the patient , we decided to start single infusion of 60 mg drug for her .
( in a 3-month period , patient received three infusions of 60 mg pamidronate ) .
after the second infusion , all the clinical and laboratory indices of the patient resolved completely .
disease activity index decreased to less than 2.6 ( das28 < 2.6 ) ( table 1 ) .
das28 and changes of its components during the pamidronate infusion courses ( first case ) by ameliorating of the joint tenderness and swelling , we discontinued cyclosporine and tapered other drugs gradually .
after three months of the last drug injection , the disease was under control by 7.5 mg of oral methotrexate per week and 1 gram of oral sulfasalazine per day .
in alzahra university hospital of isfahan , a 23-year - old homemaker suffered from rheumatoid arthritis since 2007 , was addmitted . in the disease course
, she had right wrist , elbows , shoulders , jaw , knees , and ankles involvement . in the laboratory examinations , she had a negative rheumatoid factor and anti - ccp , elevated esr ( 87 mm / h ) and crp ( 45 mg / l ) , and leukocytosis ( 13.4  10/ul ) . in the disease course , she was under the treatment of oral methotrexate ( 10 mg / week ) , sulfasalazine ( 2000 mg / day ) , naproxen ( 500 mg / day ) , and prednisolone ( 7.5 mg / day ) .
this patient , as the previous case , could not afford biologic drugs . in this regrad , we started oral cyclosporine a ( 3mg / kg ) due to refractoriness to conventional dmards .
after three weeks , patient felt better and disease activity index , esr , crp and leukocytosis improved .
however , after the dose reduction in each time , clinical and laboratory signs of disease relapsed . in this respect , after signing the inform consent by the patient , we decided to start intravenous pamidronate 60 mg per month until three months .
after four weeks , laboratory and clinical signs of the patient decreased and after eight weeks , the entire patient 's joint tenderness improved .
das28 and changes of its components during the pamidronate infusion courses ( second case ) even so , we gradually started to tapered drugs .
after 3 months of the last infusion , the patient only received one - gram oral sulfasalazine per day and other drugs were discontinued .
rheumatoid arthritis is a disabling disease that in some cases is refractory to conventional dmards .
rheumatoid factor is positive in most of the cases , but some cases are seronegative and resistant.3 biologic drugs most commonly are used for refractory cases to conventional dmards,6 but they are expensive .
pamidronate is a cheap interavenous bisphosphonate that has some anti - inflammatory properties by increasing apoptosis of monocytes.2 we reported two cases of severe seronegative ra that responded to this drug . by this report
, we can schedule a more extensive research in this subject to identify the useful property of pamidronate .
ms and pm carried out the design and coordinated the study , participated in data collection and prepared the manuscript .
pamidronate is a bisphosphonate derivative that can inhibit bone resorption by actions on osteoclasts and increase bone density in spite of treatment with steroids . 
 this drug has the anti - inflammatory effect by increase apoptosis of monocytes 
 . 5 - 10 percent of rheumatoid arthritis patients is seronegative and may be resistant to conventional disease modifying anti rheumatic drugs ( dmards ) . 
 intravenous ( iv ) pamidronate can be effective in disease control in seronegative rheumatoid arthritis . 
 we report two cases of seronegative and drug resistant rheumatoid arthritis that favorably responds to pamidronate .