Bisphosphonate Use May be Associated With an Increased Risk of Periprosthetic Hip Fracture.

BACKGROUND: Osteoporosis is common among patients undergoing primary total hip arthroplasty (THA). This study aimed to evaluate the effect of bisphosphonate treatment on osteoporotic patients undergoing primary THA. METHODS: Using a national database, 30,137 patients who had osteoporosis before primary elective THA were identified during 2010 to 2020. Patients undergoing nonelective THA and those using corticosteroids or other medications for osteoporosis were excluded. Bisphosphonate users and bisphosphonate naïve patients were matched 1:1 based on age, sex, Elixhauser comorbidity index, and a history of obesity, rheumatoid arthritis, tobacco use, and alcohol abuse. Kaplan-Meier and multivariate analyses were used to compare 2-year outcomes between groups. RESULTS: Among matched cohorts of 9,844 patients undergoing primary THA, bisphosphonate use was associated with a significantly higher 2-year rate of periprosthetic fracture (odds ratio 1.29, 95% confidence interval 1.04 to 1.61, P = .022). There was a trend toward increased risk of any revision with bisphosphonate use (odds ratio 1.19, confidence interval 1.00 to 1.41, P = .056). Rates of infection, aseptic loosening, dislocation, and mortality were not statistically different between bisphosphonate users and bisphosphonate-naïve patients. CONCLUSION: In osteoporotic patients, bisphosphonate use before primary THA is an independent risk factor for periprosthetic fracture. Additional longer-term data are needed to determine the underlying mechanism for this association and identify preventative measures.

HYPERCALCEMIA OF MALIGNANCY IN A CASE OF PERIPHERAL NERVE SHEATH TUMOR: ELUCIDATING THE ROLES OF SIMULTANEOUS MECHANISMS.

OBJECTIVE: Hypercalcemia of malignancy (HCM) is caused by 1 of 5 known mechanisms including systemic release of ectopic parathyroid hormone (PTH)-related protein (PTHrP), calcitriol, PTH, cytokines, or destruction of bone by osteolytic metastases. We report the first case of 2 simultaneous mechanisms for HCM in a patient with a peripheral nerve sheath tumor (PNST). METHODS: PubMed and Google Scholar searches were performed using "hypercalcemia of malignancy" as the search term. RESULTS: A 26-year-old woman with neurofibromatosis presented with worsening left hip pain. Magnetic resonance imaging showed a large left paraspinal mass, subtotal resection of which confirmed PNST. Despite chemo-radiation therapy, the tumor progressed over 16 months, requiring tumor debulking and L3-4 lumbar laminectomy. The patient developed progressive bilateral lower extremity weakness due to direct tumor invasion of the lumbosacral vertebrae with concurrent hypercalcemia. Ionized calcium was 1.47 mmol/dL (reference range is 0.95 to 1.32 mmol/dL), PTH was <4.0 pg/mL (reference range is 8 to 85 pg/mL), 25-hydroxyvitamin D was 14 ng/mL, calcitriol was <8.0 pg/mL (reference range is 18 to 78 pg/mL), PTHrP was 40 pg/mL(reference range is 14 to 27 pg/mL), urinary calcium was <2.0 mg/24 hours, serum C-telopeptide was 1,008 pg/mL (reference range is 64 to 640 pg/mL), and bone-specific alkaline phosphatase was 15.7 µg/L (reference range is 4.7 to 17.8 µg/L). Her serum magnesium, phosphorus, and creatinine levels were normal. Intravenous zoledronic acid and hydration resulted in a normal ionized calcium. Additional imaging revealed extensive tumor invasion of L3-S1 vertebrae. Due to her poor response to all cancer therapies, the patient was discharged to home hospice services. CONCLUSION: HCM due to PTHrP and osteolytic metastases has not been independently reported to our knowledge in association with malignant PNST as in our patient. The therapeutic importance of characterizing the mechanism of HCM is further discussed in detail.

Hypercalcemia of Malignancy in Thymic Carcinoma: Evolving Mechanisms of Hypercalcemia and Targeted Therapies.

Here we describe, to our knowledge, the first case where an evolution of mechanisms responsible for hypercalcemia occurred in undifferentiated thymic carcinoma and discuss specific management strategies for hypercalcemia of malignancy (HCM). Case Description. We report a 26-year-old male with newly diagnosed undifferentiated thymic carcinoma associated with HCM. Osteolytic metastasis-related hypercalcemia was presumed to be the etiology of hypercalcemia that responded to intravenous hydration and bisphosphonate therapy. Subsequently, refractory hypercalcemia persisted despite the administration of bisphosphonates and denosumab indicative of refractory hypercalcemia. Elevated 1,25-dihydroxyvitamin D was noted from the second admission with hypercalcemia responding to glucocorticoid administration. A subsequent PTHrP was also elevated, further supporting multiple mechanistic evolution of HCM. The different mechanisms of HCM are summarized with the role of tailoring therapies based on the particular mechanism underlying hypercalcemia discussed. Conclusion. Our case illustrates the importance of a comprehensive initial evaluation and reevaluation of all identifiable mechanisms of HCM, especially in the setting of recurrent and refractory hypercalcemia. Knowledge of the known and possible evolution of the underlying mechanisms for HCM is important for application of specific therapies that target those mechanisms. Specific targeting therapies to the underlying mechanisms for HCM could positively affect patient outcomes.

Primary care use of FRAX: absolute fracture risk assessment in postmenopausal women and older men.

Osteoporosis-related fractures (low-trauma or fragility fractures) cause substantial disability, health care costs, and mortality among postmenopausal women and older men. Epidemiologic studies indicate that at least half the population burden of osteoporosis-related fractures affects persons with osteopenia (low bone density), who comprise a larger segment of the population than those with osteoporosis. The public health burden of fractures will fail to decrease unless the subset of patients with low bone density who are at increased risk for fracture are identified and treated. Risk stratification for medically appropriate and cost-effective treatment is facilitated by the World Health Organization (WHO) FRAX algorithm, which uses clinical risk factors, bone mineral density, and country-specific fracture and mortality data to quantify a patient's 10-year probability of a hip or major osteoporotic fracture. Included risk factors comprise femoral neck bone mineral density, prior fractures, parental hip fracture history, age, gender, body mass index, ethnicity, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis. FRAX was developed by the WHO to be applicable to both postmenopausal women and men aged 40 to 90 years; the National Osteoporosis Foundation Clinician's Guide focuses on its utility in postmenopausal women and men aged >50 years. It is validated to be used in untreated patients only. The current National Osteoporosis Foundation Guide recommends treating patients with FRAX 10-year risk scores of > or = 3% for hip fracture or > or = 20% for major osteoporotic fracture, to reduce their fracture risk. Additional risk factors such as frequent falls, not represented in FRAX, warrant individual clinical judgment. FRAX has the potential to demystify fracture risk assessment in primary care for patients with low bone density, directing clinical fracture prevention strategies to those who can benefit most.

Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw.

Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide cross-link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated.

Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry.

Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis, assess the risk of fracture, and monitor changes in BMD over time. Because biological changes in BMD are usually small in proportion to the error inherent in the test itself, interpretation of serial BMD tests depends on knowledge of the smallest change in BMD that is beyond the range of error. This value, called the least significant change (LSC), varies according to the instrument used, the patient population being tested, the measurement site, the skill of the technologist at positioning the patient and analyzing the test, and the confidence interval used in the calculation. The precision and LSC values provided by the manufacturer cannot be applied to clinical bone densitometry centers because of the differences in the patients being tested and the technologist performing the test. Because harmful errors in clinical management may occur from incorrectly interpreting serial BMD tests, it is recommended that every DXA technologist conduct a precision assessment and calculate the LSC for each measurement site and DXA instrument used. Precision assessment provides direct benefit to patients by allowing clinicians to make clinical decisions based on genuine change or stability of BMD. The patient-care benefits of precision assessment outweigh the risk of exposure to trivial doses of ionizing radiation.