Assessment of gait and posture characteristics using a smartphone wearable system for persons with osteoporosis with and without falls.

We used smartphone technology to differentiate the gait characteristics of older adults with osteoporosis with falls from those without falls. We assessed gait mannerism and obtained activities of daily living (ADLs) with wearable sensor systems (smartphones and inertial measurement units [IMUs]) to identify fall-risk characteristics. We recruited 49 persons with osteoporosis: 14 who had a fall within a year before recruitment and 35 without falls. IMU sensor signals were sampled at 50 Hz using a customized smartphone app (Lockhart Monitor) attached at the pelvic region. Longitudinal data was collected using MoveMonitor+ (DynaPort) IMU over three consecutive days. Given the close association between serum calcium, albumin, PTH, Vitamin D, and musculoskeletal health, we compared these markers in individuals with history of falls as compared to nonfallers. For the biochemical parameters fall group had significantly lower calcium (P = 0.01*) and albumin (P = 0.05*) and higher parathyroid hormone levels (P = 0.002**) than nonfall group. In addition, persons with falls had higher sway area (P = 0.031*), lower dynamic stability (P < 0.001***), gait velocity (P = 0.012*), and were less able to perform ADLs (P = 0.002**). Thus, persons with osteoporosis with a history of falls can be differentiated by using dynamic real-time measurements that can be easily captured by a smartphone app, thus avoiding traditional postural sway and gait measures that require individuals to be tested in a laboratory setting.

Bone turnover markers to monitor oral bisphosphonate therapy.

Bisphosphonates are widely used as first-line therapy to slow bone loss and decrease fracture risk in postmenopausal women with osteoporosis. Nonadherence to oral bisphosphonates diminishes the benefit of reduced bone loss and fracture risk of these medications. Strategies to enhance osteoporosis monitoring and adherence to therapy are crucial to improve outcomes. Dual-energy x-ray absorptiometry (DXA) is the gold standard for monitoring bone mineral density but is slow to detect change after initiation of oral bisphosphonate therapy. Bone turnover markers (BTMs) are by-products released during bone remodeling and are measurable in blood and urine. We review how the rapid change in BTMs can be a useful short-term tool to monitor the effectiveness of oral bisphosphonate therapy, which may ultimately improve adherence to therapy and outcomes.

Positive HLA-B27 and sacroiliitis is not always spondyloarthritis.

A 36-year-old man was treated for several years with multiple agents for ankylosing spondylitis based on positive human leukocyte antigen-B27 and sacroiliitis. He was also diagnosed with osteoporosis and hypophosphatemia. Over these years, from being an avid runner, he became dependent on a walker for ambulation. The lack of treatment response and the low phosphorus were clues that eventually led to a diagnosis of tumor-induced osteomalacia. This case discusses the importance of not solely relying on genetic markers and sacroiliitis for diagnosing ankylosing spondylitis as other conditions can cause similar presentations.

Molecular Imaging in Diagnosis of Tumor-induced Osteomalacia.

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23 (FGF23) secreted by benign mesenchymal neoplasm. Due to its nonspecific clinical presentation or lack of awareness, the diagnosis of TIO is often significantly delayed resulting in patients' prolonged physical suffering or psychological distress. Successful detection or complete surgical resection of the causative tumor typically leads to rapid resolution of symptoms or reversal of biochemical imbalance. Nuclear medicine and molecular imaging have been playing a promising role as the first-line imaging modalities in the diagnosis and localization of occult FGF23 secreting mesenchymal tumor, especially with the emerging whole-body, head-to-toe Ga68-DOTATATE PET/CT technique. Combined focused diagnostic CT and/or MRI are imperative for accurate delineation of tumor and surgical guidance.

The utility of repeat sestamibi scans in patients with primary hyperparathyroidism after an initial negative scan.

BACKGROUND: We analyzed the utility of repeated sestambi scans in patients with primary hyperparathyroidism and its effects on operative referral. METHODS: We carried out a retrospective review of patients with primary hyperparathyroidism who underwent repeated sestambi scans exclusively within our health system between 1996-2015. Patient demographic, presentation, laboratory, imaging, operative, and pathologic data were reviewed. Univariate analysis with JMP Pro v12 was used to identify factors associated with conversion from an initial negative to a subsequent positive scan. RESULTS: After exclusion criteria (including reoperations), we identified 49 patients in whom 59% (n = 29) of subsequent scans remained negative and 41% (n = 20) converted to positive. Factors associated with an initial negative to a subsequent positive scan included classic presentation and second scans with iodine subtraction (P = .04). Nonsurgeons were less likely to order an iodine-subtraction scan (P < .05). Fewer patients with negative imaging were referred to surgery (33% vs 100%, P = .005), and median time to operation after the first negative scan was 25 months (range 1.4-119). Surgeon-performed ultrasonography had greater sensitivity and positive predictive value than repeated sestamibi scans. CONCLUSION: Negative sestambi scans decreased and delayed operative referral. Consequently, we identified several process improvement initiatives, including education regarding superior institutional imaging. Combining all findings, we created an algorithm for evaluating patients with primary hyperparathyroidism after initially negative sestamibi scans, which incorporates surgeon-performed ultrasonography.

Self-monitoring of blood glucose: Advice for providers and patients.

Self-monitoring of blood glucose is a critical element in diabetes management. Providers must determine if and when patients are to perform glucose self-monitoring, set blood glucose targets, and help patients to interpret the results. Patients have a variety of continually evolving meters, supplies, and technology from which to choose. Making sense of these expectations and options is perhaps the greatest challenge for providers and patients. Working together, healthcare providers and certified diabetes educators can ensure that people with diabetes get the most out of self-monitoring of blood glucose.

A pilot study investigating the effect of parathyroidectomy on arterial stiffness and coronary artery calcification in patients with primary hyperparathyroidism.

BACKGROUND: Arterial stiffness (AS) and coronary artery calcification (CAC) are predictors of cardiovascular risk and can be measured noninvasively. The aim of this study was to analyze the effects of parathyroidectomy on AS and CAC in patients with primary hyperparathyroidism (PHP). METHODS: This prospective, institutional review board-approved study included 21 patients with PHP, who underwent parathyroidectomy. Before and 6 months after parathyroidectomy, AS was assessed by measuring central systolic pressure (CSP), central pulse pressure, augmentation pressure (AP), and augmentation index (AIx); the CAC score (Agatston) was calculated on noncontrast computed tomography. AS parameters were compared with unaffected controls from donor nephrectomy database. RESULTS: Preoperative CSP and AIx parameters in PHP patients were higher than those in donor nephrectomy patients (P = .004 and P = .039, respectively). Preoperative total CAC score was zero in 15 patients (65%) and ranged from the 72nd to the 99th percentile in 6 patients (26%). Although there were no changes in CAC or AS after parathyroidectomy on average, there was variability in individual patient responses on AS. CONCLUSION: This pilot study demonstrates that CAC is not altered in PHP patients at short-term follow-up after parathyroidectomy. The heterogeneous changes in AS after parathyroidectomy warrant further investigation in a larger study with longer follow-up.

Bone mineral density testing: is a T score enough to determine the screening interval?

To find the rational intervals for bone mineral density screening, Gourlay et al (N Engl J Med 2012; 366:225-233) used T scores to calculate the time required for women age 67 and older with normal bone mineral density or osteopenia to progress to osteoporosis. They estimated that the screening interval for women with normal bone mineral density or mild osteopenia (T score -1.49 or higher) could be as long as 15 years. However, the investigators focused mainly on T scores and when these scores reached -2.5. In our opinion, the testing interval should be guided by an assessment of clinical risk factors and not just baseline T scores.

Risk of thromboembolic events in patients with prolactinomas compared with patients with nonfunctional pituitary adenomas.

Prolactin has been proposed as a potent coactivator of platelet aggregation, possibly contributing to thromboembolic events. The objective of the study was to evaluate the relationship between prolactinoma and deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accident (CVA). Subjects were identified from a prospectively maintained pituitary database at the Cleveland Clinic. We retrospectively reviewed the charts of 544 subjects: 347 patients with prolactinomas (prolactinoma group) and 197 patients with nonfunctional pituitary adenomas (control group). Main outcome measures were DVT, PE and CVA. We found that 19 (5.5%) patients in the prolactinoma group and five (2.5%) patients in the control group had documented DVT, PE, or CVA, but this difference was not significant (p = 0.109). However, the mean initial prolactin level was higher at the time of diagnosis among prolactinoma patients than among controls (815.23 ng/ml vs. 15.90 ng/ml; p < 0.001). Among prolactinoma patients, 15 (5.5%) of 275 patients who underwent medical treatment (with cabergoline, bromocriptine, pergolide and/or other drug) and 4 (5.6%) of 72 patients who underwent transsphenoidal surgery had documented DVT, PE, or CVA, which suggests that dopaminergic therapy did not influence the risk of thromboembolic events. Hyperprolactinemia per se does not appear to predispose to a hypercoagulable state.

Hyperandrogenism in a postmenopausal woman: diagnostic and therapeutic challenges.

OBJECTIVE: To describe a postmenopausal woman with severe hyperandrogenism who responded dramatically to a gonadotropin-releasing hormone (GnRH) agonist. METHODS: Detailed clinical and laboratory findings are presented, and the pertinent literature is reviewed. RESULTS: A 53-year-old postmenopausal woman with end-stage renal disease, who had undergone kidney transplantation, was referred because of high serum testosterone levels. She presented with worsening acne and hirsutism for the previous 2 years. Her medications included prednisone (7.5 mg every other day). On examination, mild facial acne and hirsutism but no virilizing features were noted. Laboratory results showed generous postmenopausal gonadotropin levels and markedly elevated total and free testosterone levels, which failed to suppress with a 2-day low-dose dexamethasone test. Transvaginal ultrasonography and a computed tomographic scan failed to identify an ovarian or adrenal abnormality. Administration of a GnRH agonist (Depo-Lupron) resulted in a dramatic decline in follicle-stimulating hormone, luteinizing hormone, and testosterone levels after 1 month, which persisted during the course of 11 months of therapy. The source of marked hyperandrogenism in postmenopausal women represents a diagnostic challenge. The absence of a tumor on diagnostic imaging and the inability to perform catheterization studies confound the problem. Androgen levels did not suppress with glucocorticoids. We reasoned that a clear response to a GnRH agonist would indicate a nontumorous ovarian source of hyperandrogenism. Regrettably, the literature has described cases of ovarian tumors and, rarely, adrenal adenomas that are responsive to gonadotropins. CONCLUSION: The striking improvement in a postmenopausal woman with severe hyperandrogenism by means of GnRH agonist therapy demonstrates its potential use in poor surgical candidates without necessarily delineating the source of androgen excess.

Clinical utility of waist circumference in predicting all-cause mortality in a preventive cardiology clinic population: a PreCIS Database Study.

Although obesity is a risk factor for mortality, it is unclear whether waist circumference (WC) is a better predictor of mortality than BMI in a clinical setting of patients at high risk for coronary artery disease (CAD). Thus, we compared the association between WC and BMI with all-cause mortality in relation to traditional CAD risk factors in a high-risk cohort. Study population included 5,453 consecutive new patients seen between 1996 and 2005 for management of CAD risk factors in a preventive cardiology clinic. Mortality was determined from the Social Security Death Index. There were 359 deaths over a median follow-up of 5.2 years. Mortality was greater in high (>102 cm in men and >88 cm in women) vs. normal WC in both genders (P < 0.01). The unadjusted Cox proportional hazard ratio (HR) for continuous WC (per cm) was 1.02 (P < 0.001) in both genders and remained significant after adjustment for CAD risk factors (HR = 1.01 in men, HR = 1.03 in women, both P < 0.05). BMI did not associate statistically with mortality. WC associated with diabetes mellitus (DM) and CAD prevalence (P < 0.001). BMI associated only with DM (P < 0.001) and this association disappeared when WC was added to the model. We conclude that WC is an independent predictor of all-cause mortality in a preventive cardiology population. These data affirm the clinical importance of WC measurements for mortality, DM, and CAD risk prediction and suggest that obesity-specific interventions targeting WC in addition to traditional risk factor management may favorably impact these outcomes.

Teriparatide treatment in adult hypophosphatasia in a patient exposed to bisphosphonate: a case report.

We describe the case of a woman with hypophosphatasia previously exposed to bisphosphonate and subsequently treated with teriparatide (recombinant human PTH 1-34).A Caucasian woman sustained bilateral femur stress fractures when she was fifty years old, which widened despite use of calcium, vitamin D and risedronate for 2.5 years and required intramedullary rods for stabilization. Hypophosphatasia was diagnosed in the interim due to low serum alkaline phosphatase (ALP) (ALP 20 IU/L; normal (N), 40-150 IU/L) and high pyridoxal 5' phosphate (3400 nmol/L; N 18-175 nmol/L). She was referred for further management. On presentation, she had significant fracture site pain and generalized bone pain (weight bearing and non-weight bearing) - making her walker dependent at home and wheel chair dependent outside home.She could not sleep at night due to discomfort when she moved. Daily teriparatide injections, 20 mcg subcutaneously were prescribed.At 8-weeks follow-up, fracture site pain, weight-bearing and non weight-bearing pain improved significantly allowing ambulation for prolonged periods without assistance. She slept at night without discomfort. Improvement persisted during her entire treatment period. Radiographs taken at 4 and 16 months of treatment demonstrated healing of femur fractures.Biochemically, mean urine cross-link-N-telopeptide increased 11% as compared to her base-line, while bone specific alkaline phosphatase did not increase as expected.In conclusion, we observed an uncoupling of bone formation and resorption markers during her treatment period in the face of notable clinical and radiological improvement. Off-label use of teriparatide may help patients with hypophosphatasia.

Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk.

Pramlintide is a synthetic version of the naturally occurring pancreatic peptide called amylin. Amylin and pramlintide have similar effects on lowering postprandial glucose, lowering postprandial glucagon and delaying gastric emptying. Pramlintide use in type 1 and insulin requiring type 2 diabetes mellitus (DM) is associated with modest reductions in HbAlc often accompanied by weight loss. Limited data show a neutral effect on blood pressure. Small studies suggest small reductions in LDL-cholesterol in type 2 DM and modest reductions in triglycerides in type 1 DM. Markers of oxidation are also reduced in conjunction with reductions in postprandial glucose. Nausea is the most common side effect. These data indicate that pramlintide has a role in glycemic control of both type 1 and type 2 DM. Pramlintide use is associated with favorable effects on weight, lipids and other biomarkers for atherosclerotic disease.