Clinical Characteristics and Fracture Patterns Among Postmenopausal Women with Isolated Osteoporosis at the Forearm.

Patients found to have isolated osteoporosis at the 1/3 radius (1/3RO) represent a therapeutic dilemma. It is unknown whether 1/3RO is associated with an increased risk of fragility fractures, and is therefore unclear whether these patients should be treated similarly to those with osteoporosis at central sites. This retrospective study investigated the clinical significance of 1/3RO by comparing medical history, fracture prevalence, areal BMD, and Trabecular Bone Score in postmenopausal women with 1/3RO (n = 107) to age-matched women with osteoporosis at the hip and/or spine (PMO, n = 214), and to controls without osteoporosis at any site (n = 214). We then compared the clinical and densitometric characteristics among women with 1/3RO according to fracture history. The mean age of the 535 women included in the study was 71 ± 8 yr. Women with 1/3RO had BMD in the osteopenic range at all other sites (mean spine T-score = -1.0, total hip = -1.4, femoral neck = -1.7). Women with 1/3RO reported similar calcium and vitamin D intake, prevalence of primary hyperparathyroidism, chronic kidney disease, and other comorbidities compared to the other groups. The prevalence of an osteoporotic fracture of the spine, hip, wrist, or humerus tended to be higher among women with PMO compared to 1/3RO or controls (PMO: 31%, 1/3RO: 21%, Controls: 23%, p = 0.07). Among women with 1/3RO, fracture prevalence was related to older age. No other clinical characteristic distinguished women with and without fracture. Neither BMD at other sites nor TBS differed according to fracture history. Among postmenopausal women with 1/3RO, those who are older are at an increased risk of fracture, even when T-scores at other sites are well above the osteoporosis threshold. Additional research is needed to confirm our results, and to assess whether treatment should be considered to reduce fracture risk in older women with 1/3RO.

Perioperative Glucocorticoids in Patients With Rheumatoid Arthritis Having Total Joint Replacements: Help or Harm?

OBJECTIVE: The optimal strategy for perioperative glucocorticoid (GC) management in patients with rheumatoid arthritis (RA) on chronic GCs is unknown. Although there is a concern for hypotension if inadequate doses are used, higher GC exposure may increase perioperative complications. We aimed to investigate the relationships between perioperative GCs with hemodynamic instability and short-term postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) in patients with RA. METHODS: This retrospective study included patients with RA who underwent THA and TKA. GC exposure was assessed by the total cumulative dose (in prednisone equivalents) during hospitalization. Perioperative complications and hypotension were assessed. RESULTS: Of 432 patients, 387 (90%) received supraphysiologic perioperative GC. Thirty percent of patients were using chronic GCs (mean daily dose, 7 ± 4 mg). Half (54%) underwent TKA. The median age was 65 years, and 79% were women. The median cumulative GC dose during hospitalization was 37 mg (interquartile range, 27-53.3). A lower cumulative dose of GC did not increase odds of hypotension during hospitalization (unadjusted odds ratio, 1.00 [95% confidence interval, 0.99-1.01]; P = 0.66)]. However, postoperative complications were higher among patients who received higher cumulative doses after adjustment for age, body mass index, home GC use, smoking, and Charlson Comorbidity Index. Risk of short-term complications increased by 8.4% (P = 0.017) for every 10-mg increase in GC dose. CONCLUSION: A lower GC dose was not associated with increased hypotension. However, patients with higher GC exposure were more likely to have hyperglycemia and other complications. These findings suggest that harms may be associated with high perioperative GC doses. Further research is needed to determine the optimal perioperative regimen for patients with RA.

Metformin-induced weight loss in patients with or without type 2 diabetes/prediabetes: A retrospective cohort study.

It is unknown whether weight loss outcomes differ with metformin monotherapy in patients with obesity with or without type 2 diabetes (T2DM)/prediabetes (PreDM). In this retrospective study, 6- or 12-month weight loss outcomes were compared in 222 patients with or without T2DM/preDM who completed metformin monotherapy. Average weight loss was similar between groups, euglycemic vs. T2DM/preDM (6 months: 6.5 [6.0%] vs. 6.5 [6.1%] p = 0.97; 12 months: 7.4 [6.2%] vs. 7.3 [7.7%], p = 0.92). Categorical weight losses (≥5% and ≥10% of baseline weight) were also similar. Comparable clinically significant weight loss was achieved with metformin monotherapy in patients with obesity with or without T2DM/PreDM.

Bone Mineral Density: Clinical Relevance and Quantitative Assessment.

Bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry (DXA) is an internationally accepted standard-of-care screening tool used to assess fragility-fracture risk. Society guidelines have recommended which populations may benefit from DXA screening and the use of the fracture risk assessment tool (FRAX) to guide decisions regarding pharmacologic treatment for osteoporosis. According to the U.S. National Osteoporosis Foundation guidelines, postmenopausal women and men at least 50 y old with osteopenic BMD warrant pharmacologic treatment if they have a FRAX-calculated 10-y probability of at least 3% for hip fracture or at least 20% for major osteoporotic fracture. Patients with osteoporosis defined by a clinical event, namely a fragility fracture, or with an osteoporotic BMD should also be treated. Patients who are treated for osteoporosis should be monitored regularly to track expected gains in BMD by serial DXA scans. With some drug therapies, BMD targets can be reached whereby further improvements in BMD are not associated with further reductions in fracture risk. Although reaching this target might suggest a stopping point for therapy, the reversibility of most treatments for osteoporosis, except for the bisphosphonates, has dampened enthusiasm for this approach. In the case of denosumab, it is now apparent that stopping therapy at any point can lead to an increase in multiple-fracture risk. For patients who do not respond to antiosteoporosis pharmacologic therapy with an improvement in BMD, or who have an incident fragility fracture on therapy, secondary causes of osteoporosis or non-compliance with medical therapy should be considered.

Calcitriol Elevation Is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors.

BACKGROUND: Hypercalcemia of malignancy (HCM) is a common complication of advanced cancer. PTH-independent HCM may be mediated through different mechanisms: (1) humoral HCM, caused by the secretion of PTH-related peptide (PTHrP), (2) local osteolysis resulting from metastatic lesions, and (3) calcitriol-mediated hypercalcemia. Calcitriol-mediated HCM in patients with nonlymphomatous solid tumors is thought to be rare. METHODS: We performed a retrospective chart review from 2008 to 2017 to characterize further patients at our institution with solid tumors who had HCM with concomitant elevations in calcitriol. Patients with PTH-dependent hypercalcemia and patients with evidence of granulomatous disease were excluded, as were patients with hematologic malignancies. We hypothesized that patients with HCM and elevated calcitriol levels would respond less favorably to treatment with antiresorptive therapy compared with patients with HCM but without calcitriol elevation. We also aimed to assess mortality and determine if PTHrP and phosphorus levels correlate with calcitriol because both factors may alter calcitriol levels. RESULTS: Of 101 eligible patients, calcitriol was elevated in 45 (45%). PTHrP was elevated in 76% of patients with elevated calcitriol compared with 52% of patients without calcitriol elevation. The mean PTHrP value did not differ between patients with HCM and elevated calcitriol (36.3 ± 22 pg/mL) and those without calcitriol elevation (37.4 ± 19 pg/mL). Those with elevated calcitriol levels generally did not respond completely to antiresorptive treatment (80% incomplete response rate), whereas most patients without an elevation in calcitriol responded well to antiresorptive treatment (78% response rate: P < .001). There was no significant difference in the percentage of patients with metastatic bone disease among the 2 groups (49% vs. 55%, respectively). There was no difference in mortality between the 2 groups (P = .14). A weak but significant negative correlation was found between phosphorus and calcitriol (Pearson r = -0.261, P = .016). This correlation was only significant in patients without calcitriol elevation (Pearson r = -0.4, P = .0082). Also, a significant negative correlation was found between PTHrP and phosphorus, again only in patients without calcitriol elevation. DISCUSSION: In the setting of HCM, patients with calcitriol elevation are much less likely to respond to antiresorptive therapy than patients without calcitriol elevation. Because calcitriol elevation did not appear to be correlated with hypophosphatemia or elevated PTHrP, it would appear that calcitriol production under these conditions is autonomous, and not subject to normal physiological controls. These observations indicate that calcitriol elevations in patients with HCM have clinical significance.

Antiresorptive agents' bone-protective and adjuvant effects in postmenopausal women with early breast cancer.

Potent antiresorptive drugs (bisphosphonate and denosumab) are often used to protect bone health in postmenopausal breast cancer patients. In addition, clinical trials have shown that these drugs increase disease-free survival, though the mechanism of adjuvant benefit is largely unknown. Here we review the bone health and adjuvant data for both classes of antiresorptive drugs and highlight differences in their pharmacology. Inhibition of bone resorption is vitally important to protect against osteoporotic fractures, and may also contribute to adjuvant survival benefits by making the bone microenvironment less amenable to breast cancer metastasis. After a course of therapy, stoppage of bisphosphonates yields a persistent antiresorptive effect, whereas discontinuation of denosumab causes a rebound increase in bone resorption markers and a loss of bone mineral density to baseline levels. Whether the potential adjuvant benefits of denosumab are also rapidly lost after drug discontinuation deserves further investigation.

Lower Spine Volumetric Bone Density in Patients With a History of Epidural Steroid Injections.

Context: Epidural steroid injections (ESIs) are a common, effective treatment of lumbar radiculopathy and sciatica. Although the negative skeletal effects of oral glucocorticoids are well established, little is known about the impact of ESI on bone quality. Objective: To investigate the relationship between ESI exposure and volumetric bone mineral density (vBMD) at the lumbar spine (LS) using central quantitative CT. Design: Retrospective study. Setting: University hospital outpatient facility. Patients: All patients had CT scans of the LS between 2011 and 2016. Cases received at least three ESIs prior to the date of CT (n = 121). Controls were matched for age and sex (n = 121). Main Outcome Measures: Cumulative ESI dose was calculated. vBMD was measured at T12 through L5 using QCT Pro phantomless software (MindWays). Results: Mean age of subjects was 65 ± 14 years, and 49% were women. Median number of ESIs was 4 (range: 3 to 16). Median cumulative ESI dosage was 340 mg of triamcinolone or equivalent (range: 150 to 1400 mg). Compared with controls, ESI subjects had lower vBMD at each vertebral level. Higher cumulative dose was associated with lower mean vBMD at T12 to L5 (r = -0.22, P = 0.02). Conclusions: Greater cumulative ESI dose was related to lower vBMD at the LS. To our knowledge, this is the first study to measure vBMD in patients treated with ESIs. Prospective studies are needed to confirm these findings and to help identify the best strategies for preventing bone loss in this population.

Pharmacotherapy for obesity in individuals with type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. AREAS COVERED: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes. EXPERT OPINION: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Shared retronasal identifications of vapor-phase 18-carbon fatty acids.

The long-chain 18-carbon fatty acids linoleic, oleic, and stearic acids, retronasally in vapor phase, are discriminated from blanks and each other. However, ability to linguistically identify them was unknown. To explore this, a Focus Group and then Check-All-That-Apply measures gave 9 identifiers for the 3 fatty acids plus phenylethyl alcohol (PEA) and geraniol. Next, participants selected 1 of the 9 identifiers from a computer-based display. It was found that the modal identification for linoleic acid was 23% "Rubbery" (next 18% "Oily" and "New Plastic"), oleic acid was 21% Oily (next 19% Rubbery), and stearic acid was 43% Rubbery (next 22% New Plastic), but linoleic acid received ~40% food-related identifiers. Geraniol was 96% "Lemon," and PEA was 67% "Flowers." Identifications for fatty acids differed significantly (P ≤ 0.05) from those for geraniol for most participants (86%) and from those for PEA for 59% of participants. Stearic acid identifications differed significantly from those for linoleic and oleic acids for 32% of participants. However, identification for linoleic acid differed significantly from those for oleic acid for only 14% of participants. Overall, retronasal vapor-phase stearic acid was identified differently from other 18-carbon fatty acids by a substantial minority of participants, but linoleic and oleic acids were not, suggesting that these 2 vapor-phase 18-carbon fatty acids can be identified retronasally as a group but not separately.