Pathologic Fractures in Patients With Multiple Myeloma Undergoing Bisphosphonate Therapy: Incidence and Correlation With Course of Disease

Vogel, Monika; Weisel, Katja; Maksimovic, Olga; Peters, Sebastian; Brodoefel, Harald; Claussen, Claus D.; Horger, Marius

doi:10.2214/ajr.08.2002

Cited by 17 publications

(12 citation statements)

References 15 publications

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“…Despite antitumor treatments and the use of bisphosphonates, the median risk for new fracture may be as high as 14% per year [29]. Severe pain and disability are usually treated with bed rest, bracing, radiotherapy, and analgesics, with limited benefit [30].…”

Section: Discussionmentioning

confidence: 99%

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Anselmetti

Manca

Montemurro

et al. 2011

Cardiovasc Intervent Radiol

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Purpose Percutaneous vertebroplasty (PV) is a minimally invasive procedure involving the injection of bone cement within a collapsed vertebral body. Although this procedure was demonstrated to be effective in osteoporosis and metastases, few studies have been reported in cases of multiple myeloma (MM). We prospectively evaluated the safety and efficacy of PV in the treatment of vertebral compression fractures (VCFs) resulting from MM. Materials and Methods PV was performed in 106 consecutive MM patients who had back pain due to VCFs, the treatment of which had failed conservative therapies. Follow-up (28.2 ± 12.1 months) was evaluated at 7 and 15 days as well as at 1, 3, 6, 12, 18, and every 6 months after PV. Visual analog scale (VAS) pain score, opioid use, external brace support, and Oswestry Disability Index (ODI) score were recorded. Results The median pretreatment VAS score of 9 (range 4-10) significantly (P \ 0.001) decreased to 1 (range 0-9) after PV. Median pre-ODI values of 82% (range 36-89%) significantly improved to 7% (range 0-82%) (P \ 0.001). Differences in pretreatment and posttreatment use of analgesic drug were statistically significant (P \ 0.001). The majority of patients (70 of 81; 86%) did not use an external brace after PV (P \ 0.001).

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Section: Discussionmentioning

confidence: 99%

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Anselmetti

Manca

Montemurro

et al. 2011

Cardiovasc Intervent Radiol

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“…Thus, local sites of progressive bone disease may easily be missed in everyday practice. It is a well‐known phenomenon that skeletal‐related events can progress or arise despite effective global suppression of bone resorption markers by BPs …”

Section: Discussionmentioning

confidence: 99%

“…It is a well-known phenomenon that skeletal-related events can progress or arise despite effective global suppression of bone resorption markers by BPs. (20,(40)(41)(42)(43) We suggest that a possible explanation for continued progression of bone disease despite treatment with powerful BPs such as Zol may be the result of an ineffective retention of Zol at least in some patients. Why may there be such a local insufficient binding of Zol?…”

Section: Discussionmentioning

confidence: 99%

Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

Søe

Plesner

Jakobsen

et al. 2013

Journal of Bone and Mineral Research

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Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease-specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p ¼ 0.001), and with CTX/bALP in Zol naive MM patients (p ¼ 0.012). Especially in BC patients, WBrt correlated with age (p ¼ 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate with the extent of bone disease (p ¼ 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p < 0.000), osseous lesions (p < 0.001), and the preceding Zol dosing (p < 0.005) (r 2 ¼ 0.97). Comparing bone scintigrams with CT/X-ray images showed a poor correlation between sites of active bone disease and binding of scintigraphy bisphosphonate in 36% of MM patients and in 13% of BC patients. We conclude that WBrt of Zol is primarily determined by two nondisease related factors and only one disease related, but that there may be differences in retention or drug delivery at individual sites of bone disease between MM and BC patients. In order to find the optimal dosing of Zol, these observations should be taken into account.

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“…(1,2) MM is associated with bone destruction and high fracture rates primarily in the vertebra, (3,4) which leads to severe pain, loss of mobility, and neurological complications. (3,(6)(7)(8) Assessment of bone fragility in MM patients is of particular importance in order to make a decision on whether to refer to surgical treatment, vertebroplasty, or radiotherapy. (3,(6)(7)(8) Assessment of bone fragility in MM patients is of particular importance in order to make a decision on whether to refer to surgical treatment, vertebroplasty, or radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…This results from diffuse or osteolytic lesions that occur in approximately 80% of patients, (5) and contributes to increased morbidity and mortality, as well as reduced quality of life. (3,(6)(7)(8) Assessment of bone fragility in MM patients is of particular importance in order to make a decision on whether to refer to surgical treatment, vertebroplasty, or radiotherapy. (9,10) This assessment is currently based on determining the number or size of focal lesions (10,11) or cortical erosion (12) from radiographs; however, these methods do not consider the biomechanical aspects of the vertebral body and therefore may not sufficiently identify those patients requiring intervention.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling

Campbell

Peña

Giravent

et al. 2017

Journal of Bone and Mineral Research

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Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T (T if T was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (-15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (-21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (-27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R = 0.57, yield force: R = 0.59, work to yield: R = 0.50, p < 0.001), BV/TV (stiffness: R = 0.56, yield force: R = 0.58, work to yield: R = 0.49, p < 0.001), and Tb.Sp (stiffness: R = 0.51, yield force: R = 0.53, work to yield: R = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research.

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Pathologic Fractures in Patients With Multiple Myeloma Undergoing Bisphosphonate Therapy: Incidence and Correlation With Course of Disease

Abstract: Pathologic fractures in patients with multiple myeloma undergoing bisphosphonate therapy occur independently of myeloma activity and therefore should not be considered a sign of disease progression.

Cited by 17 publications

References 15 publications

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling

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