Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

Kennel, Kurt A.; Drake, Matthew T.

doi:10.1016/s0025-6196(11)60752-0

Cited by 395 publications

(287 citation statements)

References 31 publications

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“…Typically, treatments for osteoporosis include bisphosphonates and hormone therapy. However, these drugs often have detrimental side effects [4,5]. Other treatments, such as rhBMP2 therapy, focus on bone fracture healing by enhancing osteoblastogenesis [6].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of osteoporosis-related fractures is costly [3]. Current treatments for osteoporosis include bisphosphonates or hormone therapy; however these treatments exhibit some serious side effects including jaw pain, esophageal cancer, and stroke [4,5]. Therefore, a new treatment for osteoporosis with less severe side effects is needed to improve the quality of life for patients.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Nguyen¹,

Weidner²,

Schell³

et al. 2018

J Bone Marrow Res

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Background: Osteoporosis is a silent disease caused by low bone mineral density that results in bone fractures in 1 out of 2 women and 1 in 4 men over the age of 50. Although several treatments for osteopenia and osteoporosis are available, they have severe side effects and new treatments are desperately needed. Current treatments usually target osteoclasts and inhibit their activity or differentiation. Treatments that decrease osteoclast differentiation and activity but enhance osteogenesis and osteoblast activity are not available. We recently developed a peptide, CK2.3, that induces bone formation and increases bone mineral density as demonstrated by injection over the calvaria of 6 to 9-day-old mice and tail vein injection of 8-week-old mice. CK2.3 also decreased osteoclast formation and activity. However, these studies raise questions: does CK2.3 induce similar results in old mice and if so, what is the effective CK2.3 concentration and, is the bone mineral density of vertebrae of the spinal column increased as well? Methods: CK2.3 was systematically injected into the tail vein of female 6-month old mice with various concentrations of CK2.3: 0.76 μg/kg, 2.3 μg/kg, or 6.9 μg/kg per mice. Mice were sacrificed one week, two weeks, and four weeks after the first injection. Their spines and femurs were collected and analyzed for bone formation. Results: Femur and lumbar spine analyses found increased bone mineral density (BMD) and mineral apposition rate, with greater stiffness observed in femoral samples four weeks after the first injection. Histochemistry showed that osteoclastogenesis was suppressed in CK2.3 treated senile mice. Conclusions: For the first time, this study showed the increase of lumbar spine BMD by CK2.3. Moreover, it showed that enhancement of femur BMD was accompanied by increased femur stiffness only at medium concentration of CK2.3 four weeks after the first injection indicating the maintenance of bone’s structural integrity by CK2.3.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Nguyen¹,

Weidner²,

Schell³

et al. 2018

J Bone Marrow Res

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“…Future analyses will focus on assessing skeletal-related events at multiple myeloma diagnosis and during follow-up. Lastly, there are several known risks associated with bisphosphonate use [26, 27] that were not captured in the OSCER database, and therefore cannot be reported in our study.…”

Section: Discussionmentioning

confidence: 99%

Patterns of bisphosphonate treatment among patients with multiple myeloma treated at oncology clinics across the USA: observations from real-world data

Kim

Hernandez

Cyprien³

et al. 2018

Support Care Cancer

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PurposeCurrent guidelines recommend that intravenous bisphosphonates be initiated in all patients with multiple myeloma for management of bone disease. The objective of this study was to describe real-world bisphosphonate treatment patterns.MethodsThis was a retrospective observational study using oncology electronic health record (EHR) data contained in Amgen’s Oncology Services Comprehensive Electronic Records (OSCER) database, generated by Flatiron Health (New York, NY), representing over 1.5 million US oncology patients. Patients were newly diagnosed with multiple myeloma between January 1, 2009 and April 30, 2016. Timing of bisphosphonate administration, frequency, schedule, changes in dosing schedule, and discontinuations were calculated. Bisphosphonate treatment relative to renal function and anti-multiple myeloma therapy regimens were also assessed.ResultsA total of 11,112 patients were enrolled in the study with a median follow-up of 687 days. Sixty-three percent received ≥ 1 bisphosphonate administration, primarily every 4 weeks (67.7%). Mean time from diagnosis to bisphosphonate administration was 106 days (median, 29). Most patients (58.2%) initiated treatment in first year after diagnosis and about half (51.9%) either discontinued or changed dosing. Patients with poorer renal function by estimated glomerular filtration rate (eGFR) stage at baseline were less likely to receive bisphosphonates (eGFR stage 5 vs 1: 24 vs 72%) and more likely to have delayed initiation of bisphosphonate treatment from diagnosis (eGFR stage 5 vs 1: median 70 vs 25 days).ConclusionsReal-world data from US oncology practices indicate that many patients with multiple myeloma may not receive optimal therapy for bone disease, particularly those with renal impairment.Electronic supplementary materialThe online version of this article (10.1007/s00520-018-4133-1) contains supplementary material, which is available to authorized users.

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“…7 The first major adverse side effect of bisphosphonate therapy, BON, was described in a cohort of patients who presented with painful, necrotic, and exposed maxillary or mandibular bone after dental extractions. 1 Today, the major risk factors for development of BON include long-term IV administration of pamidronate (Aredia) or zoledronic acid (Zometa), concomitant use of glucocorticoids, and pre-existing dental caries and poor oral hygiene.…”

Section: Discussionmentioning

confidence: 99%

Maxilla Osteonecrosis: A Differential Diagnosis in Patients with Metastatic Cancer on Bisphosphonates

et al. 2016

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Bisphosphonate-induced osteonecrosis (BON) of the mandible and/or maxilla is an increasingly recognized, though still rare, complication of bisphosphonate therapy. In the present case, the patient presented with a seven-month history of maxillary sinusitis and pain, and was originally diagnosed with a bony metastasis from her primary breast cancer. However, surgical excision and biopsy led to a diagnosis of BON of the maxilla. As bisphosphonates are often prescribed for patients with metastatic disease, it is important to recognize that BON may present similarly to bony metastases.

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Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

Cited by 395 publications

References 31 publications

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice

Patterns of bisphosphonate treatment among patients with multiple myeloma treated at oncology clinics across the USA: observations from real-world data

Maxilla Osteonecrosis: A Differential Diagnosis in Patients with Metastatic Cancer on Bisphosphonates

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