Arch Osteoporos (2015) 10:9 DOI 10.1007/s11657-015-0213-8
CASE REPORT
Risedronate as an intra-abdominal sepsis mimic: a case report Sonali Shah & Cameron Jeremiah & Douglas Johnson & Scott Baker
Received: 11 February 2015 / Accepted: 27 February 2015 # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
Abstract Summary This case report highlights the potential severity of bisphosphonate-associated reactions. Case report A 76-year-old lady underwent several hospital admissions for investigation of fever associated with rigors, abdominal pain, and vomiting. Discussion Despite multiple investigations, no cause was found, but the timing of the symptoms coincided with monthly risedronate administration. Keywords Bisphosphonates . Osteoporosis . Risedronate . Side effects . Pyrexia of unknown origin . Intra-abdominal sepsis
Introduction Osteoporosis is a common disease associated with high morbidity, mortality, and health-care costs. Bisphosphonates are the first-line therapy for treatment of osteoporosis [1]. While they are usually well tolerated, gastrointestinal side effects are reported in around 25 % of subjects using risedronate [2]. Other side effects include an acute-phase reaction that is more commonly seen with intravenous bisphosphonate S. Shah (*) : D. Johnson : S. Baker Austin Health, 145 Studley Road, Heidelberg, Australia e-mail: [email protected] D. Johnson e-mail: [email protected] S. Baker e-mail: [email protected] C. Jeremiah Northern Health, 185 Cooper Street, Epping, Australia e-mail: [email protected]
administration. The frequency of acute-phase reactions has been observed to decrease with repeated administration [3]. This case highlights the potential severity of these common adverse effects.
Case report A 76-year-old Bangladeshi lady was admitted to a tertiary hospital six times in a span of 6 months with fever associated with gastrointestinal symptoms. Her past medical history included type 2 diabetes mellitus, polymyalgia rheumatica on low-dose prednisolone and methotrexate, mixed Alzheimer and vascular dementia, bronchiectasis, hypertension, and osteoporosis. She was taking monthly risedronate 150 mg for treatment of osteoporosis. She first presented six weeks after returning from Bangladesh with the acute onset of fever, rigors, nausea, diarrhea, abdominal pain, and worsening confusion. On examination, she was noted to have a sinus tachycardia and was febrile to 38.8 °C. Remaining examination did not reveal any localizing signs of infection. Given the severity of her presentation, she was treated empirically for presumed urinary tract infection with intravenous ceftriaxone. Her symptoms resolved within 48 h of admission and urine cultures remained negative. No source was identified after a basic septic screen, and she was discharged on oral antibiotics. About a month later, she represented with similar symptoms. She had four further admissions, each approximately a month apart. During her six admissions, she underwent investigations that failed to identify a source of her fevers. Each time, a septic screen including blood cultures, urine culture, and chest X-ray was unremarkable. One blood culture bottle was positive for Clostridium perfringens, which was thought to be a contaminant. A fecal sample was positive for Clostridium difficile
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antigen, but not toxin. Other tests including a QuantiFERONTB Gold assay; thick and thin blood films looking for malaria; multiple myeloma and vasculitis screens; computed axial tomography scan of the sinuses, chest, abdomen, and pelvis; gastroscopy; and colonoscopy were likewise unremarkable. Given the relation of the timing of the symptoms to risedronate administration and in the absence of objective evidence of infection or vasculitis, it was thought that her symptoms were side effects of bisphosphonate use. Further strengthening the argument, she has been symptom free since ceasing the risedronate.
raises the question of whether the potential severity of common side effects of bisphosphonates such as fever and gastrointestinal symptoms has been underappreciated. It also highlights the difficulty in diagnosing adverse effects from infrequently administered medications and raises awareness of bisphosphonate-associated reactions as a potential differential diagnosis in patients presenting with a clinical picture of intraabdominal sepsis.
Discussion
References
A randomized, double-blind, multicenter 12-month Japanese study published in 2014 compared the efficacy and side effects of a once-monthly preparation of 75 mg risedronate to a 2.5 mg once-daily dose. It showed that gastrointestinal side effects were documented in both regimens, with an incidence of 26.2 % in the 2.5 mg once-daily dose group and 30.8 % in the 75 mg once-monthly group, with no severe cases. An acute-phase reaction, defined as symptoms of influenza-like illness or pyrexia starting within 3 days of the first dose of the study drug and with a duration of 7 days or less, was documented only in the 75 mg once-monthly group, again, with no severe cases (2.1 %) [4]. Similarly, in a 2-year follow-up study in postmenopausal women comparing efficacy of a oncemonthly preparation of 150 mg risedronate to a 5 mg oncedaily dose, all events of influenza-like reactions and diarrhea were rated as mild or moderate in severity only [5]. Given that our patient had repeated admissions to hospital, this would be classified as a serious adverse effect. This case
Conflicts of interest None.
1. Royal Australian College of General Practitioners (2010) Clinical guideline for the prevention and treatment of osteoporosis in postmenopausal women and older women 2. Reginster J-Y, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R, on behalf of the Vertebral Efficacy with Risedronate Therapy (VERT) Study Group (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 11(1):83–91 3. Kennel KA, Drake MT (2009) Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 84(7): 632–638 4. Hagino H, Kishimoto H, Ohishi H, Horii S, Nakamura T (2014) Efficacy, tolerability and safety of once-monthly administration of 75 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5 mg once-daily dosage regimen. Bone 59:44– 52. doi:10.1016/j.bone.2013.10.017 5. McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou C-L, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S, Delmas P (2013) Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data. Osteoporos Int 24(1):293–299
CASE REPORT
Risedronate as an intra-abdominal sepsis mimic: a case report Sonali Shah & Cameron Jeremiah & Douglas Johnson & Scott Baker
Received: 11 February 2015 / Accepted: 27 February 2015 # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
Abstract Summary This case report highlights the potential severity of bisphosphonate-associated reactions. Case report A 76-year-old lady underwent several hospital admissions for investigation of fever associated with rigors, abdominal pain, and vomiting. Discussion Despite multiple investigations, no cause was found, but the timing of the symptoms coincided with monthly risedronate administration. Keywords Bisphosphonates . Osteoporosis . Risedronate . Side effects . Pyrexia of unknown origin . Intra-abdominal sepsis
Introduction Osteoporosis is a common disease associated with high morbidity, mortality, and health-care costs. Bisphosphonates are the first-line therapy for treatment of osteoporosis [1]. While they are usually well tolerated, gastrointestinal side effects are reported in around 25 % of subjects using risedronate [2]. Other side effects include an acute-phase reaction that is more commonly seen with intravenous bisphosphonate S. Shah (*) : D. Johnson : S. Baker Austin Health, 145 Studley Road, Heidelberg, Australia e-mail: [email protected] D. Johnson e-mail: [email protected] S. Baker e-mail: [email protected] C. Jeremiah Northern Health, 185 Cooper Street, Epping, Australia e-mail: [email protected]
administration. The frequency of acute-phase reactions has been observed to decrease with repeated administration [3]. This case highlights the potential severity of these common adverse effects.
Case report A 76-year-old Bangladeshi lady was admitted to a tertiary hospital six times in a span of 6 months with fever associated with gastrointestinal symptoms. Her past medical history included type 2 diabetes mellitus, polymyalgia rheumatica on low-dose prednisolone and methotrexate, mixed Alzheimer and vascular dementia, bronchiectasis, hypertension, and osteoporosis. She was taking monthly risedronate 150 mg for treatment of osteoporosis. She first presented six weeks after returning from Bangladesh with the acute onset of fever, rigors, nausea, diarrhea, abdominal pain, and worsening confusion. On examination, she was noted to have a sinus tachycardia and was febrile to 38.8 °C. Remaining examination did not reveal any localizing signs of infection. Given the severity of her presentation, she was treated empirically for presumed urinary tract infection with intravenous ceftriaxone. Her symptoms resolved within 48 h of admission and urine cultures remained negative. No source was identified after a basic septic screen, and she was discharged on oral antibiotics. About a month later, she represented with similar symptoms. She had four further admissions, each approximately a month apart. During her six admissions, she underwent investigations that failed to identify a source of her fevers. Each time, a septic screen including blood cultures, urine culture, and chest X-ray was unremarkable. One blood culture bottle was positive for Clostridium perfringens, which was thought to be a contaminant. A fecal sample was positive for Clostridium difficile
9
Arch Osteoporos (2015) 10:9
Page 2 of 2
antigen, but not toxin. Other tests including a QuantiFERONTB Gold assay; thick and thin blood films looking for malaria; multiple myeloma and vasculitis screens; computed axial tomography scan of the sinuses, chest, abdomen, and pelvis; gastroscopy; and colonoscopy were likewise unremarkable. Given the relation of the timing of the symptoms to risedronate administration and in the absence of objective evidence of infection or vasculitis, it was thought that her symptoms were side effects of bisphosphonate use. Further strengthening the argument, she has been symptom free since ceasing the risedronate.
raises the question of whether the potential severity of common side effects of bisphosphonates such as fever and gastrointestinal symptoms has been underappreciated. It also highlights the difficulty in diagnosing adverse effects from infrequently administered medications and raises awareness of bisphosphonate-associated reactions as a potential differential diagnosis in patients presenting with a clinical picture of intraabdominal sepsis.
Discussion
References
A randomized, double-blind, multicenter 12-month Japanese study published in 2014 compared the efficacy and side effects of a once-monthly preparation of 75 mg risedronate to a 2.5 mg once-daily dose. It showed that gastrointestinal side effects were documented in both regimens, with an incidence of 26.2 % in the 2.5 mg once-daily dose group and 30.8 % in the 75 mg once-monthly group, with no severe cases. An acute-phase reaction, defined as symptoms of influenza-like illness or pyrexia starting within 3 days of the first dose of the study drug and with a duration of 7 days or less, was documented only in the 75 mg once-monthly group, again, with no severe cases (2.1 %) [4]. Similarly, in a 2-year follow-up study in postmenopausal women comparing efficacy of a oncemonthly preparation of 150 mg risedronate to a 5 mg oncedaily dose, all events of influenza-like reactions and diarrhea were rated as mild or moderate in severity only [5]. Given that our patient had repeated admissions to hospital, this would be classified as a serious adverse effect. This case
Conflicts of interest None.
1. Royal Australian College of General Practitioners (2010) Clinical guideline for the prevention and treatment of osteoporosis in postmenopausal women and older women 2. Reginster J-Y, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R, on behalf of the Vertebral Efficacy with Risedronate Therapy (VERT) Study Group (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 11(1):83–91 3. Kennel KA, Drake MT (2009) Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 84(7): 632–638 4. Hagino H, Kishimoto H, Ohishi H, Horii S, Nakamura T (2014) Efficacy, tolerability and safety of once-monthly administration of 75 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5 mg once-daily dosage regimen. Bone 59:44– 52. doi:10.1016/j.bone.2013.10.017 5. McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou C-L, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S, Delmas P (2013) Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data. Osteoporos Int 24(1):293–299
