Efficacy of Oral Cinacalcet in Non-PTH Nonmalignant Hypercalcemia from Excess 1,25-Dihydroxyvitamin D.

Elevated 1,25-dihydroxyvitamin D (1,25(OH)2D) is a rare cause of non-parathyroid hormone (PTH)-mediated hypercalcemia seen in granulomatous disease, malignancy (most often lymphoma), or genetic mutations. Therapeutic options are limited. We report the case of a 67-year-old White man with nonmalignant, nongranulomatous, 1,25(OH)2D-mediated hypercalcemia treated successfully with cinacalcet. At presentation, he had hypercalcemia, hypercalciuria with recurrent nephrolithiasis, low PTH, elevated 1,25(OH)2D, and normal 25-hydroxyvitamin D. The 1,25(OH)2D levels were inappropriate in the setting of hypercalcemia with low PTH. Evaluations for sarcoidosis, tuberculosis, and malignancy were negative. Genetic testing showed biallelic variants in the CYP24A1 gene. Cinacalcet was trialed and showed normalization of calcium levels. On cinacalcet, biochemical indices showed a slight increase in 1,25(OH)2D and 24-hour urine calcium and mild decrease in PTH. He briefly experienced symptomatic hypocalcemia that resolved after reducing cinacalcet dose. Due to limited symptomatic benefit, he opted to stop cinacalcet. Additional follow-up showed intermittently elevated serum calcium levels after stopping cinacalcet, most recently 10.3 mg/dL. Cinacalcet may be a therapeutic option in nonmalignant, 1,25(OH)2D-mediated hypercalcemia. Further study is necessary to confirm efficacy, understand risks and benefits, and elucidate mechanism(s) of action.

Giant cell arteritis associated with intravenous zoledronic acid administration.

Bisphosphonates frequently provoke a cytokine-driven acute clinical response (ACR) characterized by fever, chills, arthralgias, and myalgias. More rarely, an association between aminobisphosphonates, such as alendronate and zoledronic acid, and rheumatologic and/or immune-mediated syndromes (RIMS) has been described. Herein we report 2 patients, one with a prior history of rheumatic disease and one without, who developed giant cell arteritis meeting the American College of Rheumatology 2022 criteria following zoledronic acid infusion. We subsequently review existing mechanistic and clinical literature supporting this link. The duration of symptoms and elevation of inflammatory markers may serve as indicators for differentiating between the more common ACR and less frequent but potentially morbid RIMS. Although the benefit of bisphosphonates will outweigh the risk of RIMS for most patients with high fracture risk, clinicians should be aware of this phenomenon to assist earlier diagnosis and treatment in affected individuals.

The Eucalcemic Patient With Elevated Parathyroid Hormone Levels.

Primary hyperparathyroidism (PHPT) is classically characterized by hypercalcemia with elevated or inappropriately normal parathyroid hormone (PTH) levels. Elevated PTH levels in the presence of normal calcium levels are not infrequently found during the evaluation of metabolic bone disorders or kidney stone disease. This can be caused by secondary hyperparathyroidism (SHPT) or normocalcemic primary hyperparathyroidism (NPHPT). NPHPT is due to autonomous parathyroid function whereas SHPT is caused by a physiologic stimulation to PTH secretion. Many medical conditions and medications can contribute to SHPT, and differentiation between SHPT and NPHPT may be difficult. Cases are presented to illustrate examples. In this paper, we review the distinction between SHPT and NPHPT as well as end organ effects of NPHPT and outcomes of surgery in NPHPT. We suggest that the diagnosis of NPHPT be made only after careful exclusion of causes of SHPT and consideration of medications that can increase PTH secretion. Further, we advise a conservative approach to surgery in NPHPT.

C11 choline PET/CT succeeds when conventional imaging for primary hyperparathyroidism fails.

BACKGROUND: Focused parathyroidectomy in primary hyperparathyroidism is possible with accurate preoperative localization. A growing body of data exists regarding the role of radio-labeled C11 choline positron emission tomography/computed tomography. In cases of nonlocalized disease, it may be a useful adjunct to ultrasound, (123)I/(99)Tc-sestamibi (I-123 sestamibi), or 4-dimensional computed tomography imaging. METHODS: Patients who received a neck and chest limited coverage C11 choline positron emission tomography/computed tomography for evaluation of primary hyperparathyroidism from 2017 to 2021 at a single institution were retrospectively reviewed. We assessed the sensitivity, positive predictive value, and false negative rate. We also compared these rates to the standard modalities of ultrasound, I-123 sestamibi, 4-dimensional computed tomography, and examined concordance rates. RESULTS: We identified 43 patients, of whom 33 had a positive C11 choline positron emission tomography/computed tomography finding. This cohort of patients had failed to localize on multiple standard imaging modalities. Twenty-five patients proceeded to surgery, 72% of whom were reoperative cases. Twenty (80%) achieved an intraoperative cure. Analysis showed that C11 choline positron emission tomography/computed tomography achieved a sensitivity of 64% (95% confidence interval 47%-82%) and positive predictive value of 72% (95% confidence interval 54%-90%). There were 5/25 (20%) false positive positron emission tomography C11 choline results found to be lymph nodes, normal parathyroid, and 1 recurrent laryngeal nerve neuroma. CONCLUSION: C11 choline positron emission tomography/computed tomography is a useful adjunct for parathyroid localization in a complex population of patients who have failed standard localization techniques including ultrasound, I-123 sestamibi, or 4-dimensional computed tomography and/or prior operations. Although routine inclusion of C11 choline positron emission tomography/computed tomography imaging may not be necessary, it may aid in preoperative localization in the reoperative setting.

Persistence and Recurrence of Hypercalcemia After Parathyroidectomy Over 5 Decades (1965-2010) in a Community-based Cohort.

BACKGROUND: There is limited long-term follow-up of patients undergoing parathyroidectomy. Recurrence is described as 4% to 10%. This study evaluated persistence and recurrence of hypercalcemia in primary hyperparathyroidism after parathyroidectomy. METHODS: Single-institution retrospective (1965-2010) population-based cohort from Olmsted County (MN) of patients undergoing surgery for primary hyperparathyroidism. Patients' demographic data, preoperative and postoperative laboratory values, clinical characteristics, surgical treatment, and follow-up were noted. RESULTS: A total of 345 patients were identified, 75.7% female, and median age 58.4 years [interquartile range (IQR): 17.6]. In all, 68% of patients were asymptomatic and the most common symptoms were musculoskeletal complaints (28.4%) and nephrolithiasis (25.6%). Preoperative median serum calcium was 11 mg/dL (IQR: 10.8-11.4 mg/dL), and median parathyroid hormone was 90 pg/mL (IQR: 61-169 pg/dL). Bilateral cervical exploration was performed in 38% and single gland resection in 79% of cases. Median postoperative serum calcium was 9.2 mg/dL (IQR: 5.5-11.3). Nine percent of patients presented persistence of hypercalcemia, and recurrence was found in 14% of patients. Highest postoperative median serum calcium was 10 mg/dL (IQR: 6-12.4), and median number of postoperative calcium measurements was 10 (IQR: 0-102). Postoperative hypercalcemia was identified in 37% of patient. Fifty-three percent were attributed to secondary causes, most commonly medications, 22%. Three percent of patients required treatment for postoperative hypercalcemia. Median time to recurrence and death were 12.2 and 16.7 years, respectively. CONCLUSION: Recurrent hypercalcemia after successful parathyroidectomy is higher than previously reported. Most cases are transient and often associated to other factors with only the minority requiring treatment. Long-term follow-up of serum calcium should be considered in patients after successful parathyroidectomy.

Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.

In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT). PHPT is typically a disease of postmenopausal women, but its prevalence and incidence vary globally and depend on a number of factors, the most important being the availability to measure serum calcium and parathyroid hormone levels for screening. In the Western world, the change in presentation to asymptomatic PHPT is likely to occur, over time also, in Eastern regions. The selection of the population to be screened will, of course, affect the epidemiological data (ie, general practice as opposed to tertiary center). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs). Clonally dysregulated overgrowth of one or more parathyroid glands together with reduced expression of CaSRs is the most important pathophysiologic basis of PHPT. The spectrum of skeletal disease reflects different degrees of dysregulated bone remodeling. Intestinal calcium hyperabsorption together with increased bone resorption lead to increased filtered load of calcium that, in addition to other metabolic factors, predispose to the appearance of calcium-containing kidney stones. A genetic basis of PHPT can be identified in about 10% of all cases. These may occur as a part of multiple endocrine neoplasia syndromes (MEN1-MEN4), or the hyperparathyroidism jaw-tumor syndrome, or it may be caused by nonsyndromic isolated endocrinopathy, such as familial isolated PHPT and neonatal severe hyperparathyroidism. DNA testing may have value in: confirming the clinical diagnosis in a proband; eg, by distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH). Mutation-specific carrier testing can be performed on a proband's relatives and identify where the proband is a mutation carrier, ruling out phenocopies that may confound the diagnosis; and potentially prevention via prenatal/preimplantation diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Routine Use of Preoperative Neck Ultrasound in Primary Hyperparathyroidism Identifies Coexisting Thyroid Disease and Improves Parathyroid Localization.

BACKGROUND: In Jan 2018, we began routinely obtaining neck ultrasound (US) with 123I/99Tc-sestamibi (MIBI) for parathyroid gland localization and to identify thyroid pathology in the setting of primary hyperparathyroidism (1HPT). The aim of this study is to assess if routine neck US is a useful adjunct to 123I/99Tc-MIBI in 1HPT. METHODS: Patients undergoing surgery for 1HPT with both 123I/99Tc-MIBI and US at our institution after implementation of routine US were reviewed. Biopsy and surgical management of thyroid pathology was evaluated. 123I/99Tc-MIBI and US results were compared to intraoperative findings to determine sensitivity and positive predictive value (PPV) for parathyroid localization. RESULTS: From January 2018 to September 2019, there were 423 patients (mean, 61 years) that met inclusion criteria (80% women). Thyroid nodules were found on US in 57%, mean size 1.3 + 0.8 cm. Fine needle aspiration (FNA) was performed in 87 patients with nodules (36%). 35 patients (8.5%) required total or partial thyroidectomy for diagnoses/treatment. Papillary thyroid cancer (PTC) was found in 3.5% of the cohort with micro-PTC 53% and PTC 1-2 cm 40%. A successful parathyroid operation for 1HPT was achieved in 98.6% of patients. Positive predictive value for localization of abnormal parathyroid glands was 97% when US and 123I/99Tc-MIBI had concordant findings. DISCUSSION: Routine use of US in 1HPT commonly identifies nodules that are benign or low-risk PTC. Ultrasound is less sensitive for parathyroid localization but when used with 123I/99Tc-MIBI, concordant imaging has a high PPV.

Survival in primary hyperparathyroidism over five decades (1965-2010) a population-based retrospective study.

CONTEXT: Survival in patients with primary hyperparathyroidism (PHPT) remains uncertain. OBJECTIVE: To update survival in patients with PHPT in a United States community population. DESIGN: Retrospective cohort study. SETTING: Community population in Rochester, Minnesota. PARTICIPANTS: Residents who met criteria for PHPT from 1965 to 2010. INTERVENTIONS: Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. MAIN OUTCOME MEASURE: The overall age and gender-adjusted survival compared to white Minnesota residents. RESULTS: We identified 1139 PHPT individuals, 76% female, with a median age of 58 years. Most were observed without parathyroidectomy (69%). The relative risk of death among the entire cohort was 0.996 (95% CI: 0.91-1.09, P = 0.935) which was not different compared to Minnesota residents. Those with maximum serum calcium level ≥ 10.8 mg/dL (0.7 mg/dL above the reference range) had an increase in mortality (RR 1.32, 95% CI: 1.10-1.58, P = 0.002). Survival among all PHPT individuals after parathyroidectomy was no different from expected (RR = 1.06, 95% CI 0.89-1.28; P = 0.508). Mortality was significantly decreased after parathyroidectomy in those with serum calcium levels ≥10.8 mg/dL (HR 0.47, 95% CI: 0.36-0.61, P < 0.001). CONCLUSIONS: Mortality in the entire cohort was not different from expected. PHPT patients with a maximum serum calcium level ≥ 10.8 mg/dL had increased mortality. Survival was improved after parathyroidectomy in those with this degree of hypercalcemia.

Hypoparathyroidism: An Uncommon Complication Associated With Immune Checkpoint Inhibitor Therapy.

As immune checkpoint inhibitor drugs are being used in the treatment of some cancers, unusual adverse events are being reported, labeled as immune-related adverse events. Various endocrinopathies related to immune-related adverse events have been described, among which hypoparathyroidism is exceedingly rare. We report a case of hypoparathyroidism induced by immune checkpoint drugs, highlighting the need for awareness of this emerging complication.

Parathyroidectomy improves hypercalciuria in patients with primary hyperparathyroidism.

BACKGROUND: Hypercalciuria is an important manifestation of primary hyperparathyroidism and may contribute to the risk of nephrolithiasis. This study examined the impact of parathyroidectomy on 24-hour urinary calcium (24-hour UCa) levels and rates of resolution of hypercalciuria after surgery. METHODS: A retrospective cohort study was performed of patients who underwent curative parathyroidectomy for primary hyperparathyroidism from 2007 to 2017. Baseline and postoperative urine and serum biochemistry levels were analyzed. The relationship between preoperative 24-hour UCa levels and the absolute decrease in postoperative UCa excretion was assessed using Spearman's rank correlation coefficient. RESULTS: Of 110 patients, 84 (76.4%) experienced a ≥20% decrease in 24-hour UCa level postoperatively. These patients had a higher baseline median 24-hour UCa level (293.5 vs 220.5 mg/24-hour; P = .001), higher baseline mean serum parathyroid hormone (106.5 vs 83; P = .05) and were more likely to have single gland disease (85.7% vs 65.4%, P = .04) compared with patients in whom 24-hour UCa excretion did not improve. Of the 28 patients (25%) who were hypercalciuric (24-hour UCa >400 mg/day) at baseline, 22 (79%) became normocalciuric postoperatively. A linear correlation was observed between preoperative 24-hour UCa levels and the decline in 24-hour UCa excretion after surgery (R2 = 0.59, P < .0001) such that the degree of improvement could be predicted using the following equation: absolute decrease in postoperative 24-hour UCa = 0.68 × preoperative 24-hour UCa-68. CONCLUSION: Parathyroidectomy reduces 24-hour UCa excretion in the majority of patients with PHPT and restores normocalciuria in 79% of patients with hypercalciuria at baseline.

Oral cinacalcet responsiveness in non-parathyroid hormone mediated hypercalcemia of malignancy.

Hypercalcemia of malignancy develops in approximately 20-30% of patients with advanced cancer and is an ominous sign. This condition is subdivided into three categories: i) humoral hypercalcemia of malignancy (80% of cases), mediated by systemic parathyroid hormone-related protein; ii) osteolytic metastases (20% of cases), mediated by inflammatory cytokines locally released by tumor cells and/or peri-tumor macrophages; and iii) ectopic production of 1,25-dihydroxyvitamin D (<1% of cases), leading to intestinal hyperabsorption of calcium and increased osteoclastic bone resorption. Humoral hypercalcemia of malignancy is seen in a variety of solid tumors, while osteolytic metastases are most common in breast cancer and multiple myeloma. Hypercalcemia of malignancy mediated by 1,25-dihydroxyvitamin D is primarily seen in lymphomas, having only rarely been reported in solid tumors. Pharmacologic management of humoral hypercalcemia of malignancy and osteolytic metastases mainly involves inhibition of bone resorption with intravenous bisphosphonates, subcutaneous denosumab, and subcutaneous calcitonin. Glucocorticoid therapy is the mainstay for management of increased 1,25-dihydroxyvitamin D. Unfortunately, management of hypercalcemia of malignancy often requires inpatient admission in the acute setting, and loss of effectiveness of antiresorptive therapy is common. We propose oral cinacalcet may be an efficacious therapy for hypercalcemia of malignancy related to elevated 1,25-dihydroxyvitamin D, and we present supporting data from two cases involving solid tumors. Furthermore, we hypothesize that this effect is primarily mediated by cinacalcet's interaction with the calcium-sensing receptor in the intestine with lesser effects at bone and kidney. Lastly, the role of 1,25-dihydroxyvitamin D in hypercalcemia malignancy may be underappreciated in solid tumors.

Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations.

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.

Rates of hypercalcemia and hyperparathyroidism among patients with porcelain gallbladder.

BACKGROUND: Porcelain gallbladder is characterized by calcification of the gallbladder wall, possibly associated chronic inflammation from cholelithiasis. It is unknown whether porcelain gallbladder is associated with higher rates of hypercalcemia and/or hyperparathyroidism compared to cholelithiasis without porcelain gallbladder. METHODS: We searched our patient database for patients with porcelain gallbladder on imaging and patients with cholelithiasis without porcelain gallbladder. We collected data on patient age, gender, calcium levels, parathyroid hormone (PTH) levels, and medications/comorbidities known to cause hypercalcemia. RESULTS: 1000 patients within our database had porcelain gallbladder on imaging. Of these, 661 (245 male) had at least one serum calcium value for analysis. These patients were matched by age and gender with 6610 patients with cholelithiasis who had at least one serum calcium value. Rates of recurrent/persistent hypercalcemia were higher among patients with porcelain gallbladder at 16.8% versus 11.1% (p < 0.01). Rates of hyperparathyroidism were also higher among porcelain gallbladder patients at 12% versus 7.5% (p < 0.01). CONCLUSION: Patients with porcelain gallbladder show higher rates of hypercalcemia and hyperparathyroidism than patients with cholelithiasis alone.

Clinical characteristics and depression score response after parathyroidectomy in primary hyperparathyroidism.

OBJECTIVE: Several studies indicate that patients with primary hyperparathyroidism (PHPT) undergoing parathyroid surgery have improvement in mood and neuropsychological functioning. The current analysis aims to examine the relationship between biochemical and clinical variables and the improvement in depression scores and in specific symptoms, after parathyroidectomy. DESIGN: A prospective observational case-control study at a referral centre. PATIENTS: Patients with PHPT undergoing parathyroidectomy (n = 88) or thyroid surgery (n = 85). MEASUREMENTS: The Patient Health Questionnaire-9 (PHQ-9) was utilized to obtain depression scores at enrolment and 12 months after surgery. The changes in PHQ-9 were analysed and correlated with baseline clinical and biochemical parameters. RESULTS: At enrolment, there was no difference between the groups in the number with a depression diagnosis (PHPT 34.1%, thyroid surgery, 35.5%, P = 0.86). However, baseline PHQ-9 scores were significantly higher in PHPT (median 7.5, range 0-27) than thyroid surgery patients (median 3.0, range 0-18, P < 0.0001). Following surgery, all PHQ-9 scores, total and symptom group (cognitive, somatic) improved and were no longer different between PHPT (total PHQ-9 median 2, range 0-16) and thyroid (median 1, range 0-14, P = 0.31) groups. Baseline parathyroid hormone level, but not calcium, had a weak relationship with change in PHQ-9 score after parathyroid surgery (P = 0.003). Baseline PHQ-9 score was correlated with change in PHQ-9 score at 12 months after parathyroid surgery (P < 0.001). CONCLUSIONS: Depression scores improve in both somatic and cognitive domains after parathyroidectomy for PHPT and baseline severity of depression predicts the response.

TRANSIENT OSTEOPOROSIS: CLINICAL SPECTRUM IN ADULTS AND ASSOCIATED RISK FACTORS.

Objective: We aimed to describe the natural history of the rare clinical syndrome of transient osteoporosis (TO) and ascertain potential risk factors. Methods: Retrospective cohort study of adults with TO at Mayo Clinic, Rochester, Minnesota, over 15 years. Adults with acute-onset joint pain worsened by weight bearing and bone marrow edema on magnetic resonance imaging were included; exclusion criteria were trauma, tumors, rheumatic diseases, avascular necrosis, infection, and hyperesthesia. Results: Thirty-three patients with TO were identified: 20 males, median age at diagnosis 47 years, and median body mass index 28 kg/m2. Median time to diagnosis was 2 months, and time to symptom resolution was 4 months. All cases involved the lower extremity, with the majority affecting the hip. Most patients (79%) had at least one possible identified risk factor. The most frequent risk factor was low bone mineral density (BMD) in 13 patients (39% of cohort). Of the 16 patients with BMD measure, 8 had low BMD at a site other than TO. The next most frequent risk factors were sudden limb overuse and more than one episode of TO, observed in 30%, followed by a disorder of bone and mineral metabolism in 27%. Conclusion: TO affects middle-age men more than women, primarily involves weight-bearing joints, and usually resolves with conservative management. Its etiology remains unclear; however, the common presence of risk factors, abnormalities in bone and mineral laboratories, and decrease in BMD suggest that systemic factors may be important in its development. Abbreviations: AVN = avascular necrosis; BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; MRI = magnetic resonance imaging; TO = transient osteoporosis.

The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report.

Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40-70%. © 2018 American Society for Bone and Mineral Research.