PurposeBone mineral density (BMD) measured with dual x-ray absorptiometry (DXA) is the clinical standard for the diagnosis of osteoporosis and prediction of bone fracture risk. In the aging skeleton, osteoporosis is often concomitantly present with degenerative joint disease (DJD).MethodsIn this study, we evaluated tissue-level changes in the differentially loaded concave (CC) and convex (CV) sides of the lumbar spine in a sample of postmenopausal women with scoliosis. We used a cumulative degeneration score to assess osteophyte formation, the severity of sclerotic morphology, and marrow changes as markers of DJD in the lumbar spine and examined the correlation between markers of DJD and BMD.ResultsMore severe osteophyte growth and sclerosis were present on the CC side of the spine. The degenerative score (DS) was higher on the CC side of the lumbar spine compared with the CV side. While CC BMD was positively correlated with CC DS and marrow, CV DS was not correlated with CV BMD. Marrow changes were correlated with DS on the CC lumbar spine.ConclusionThese results highlight the importance of mechanoadaptive as well as broader inflammatory processes in the manifestation of degenerative changes and local mineral deposition at the lumbar spine. DXA-based BMD measurement of osteoporosis need to be contextualized within the biomechanical and degenerative conditions of a joint rather than using a strict threshold cutoff.

Inhalant use disorder is a psychiatric condition characterized by repeated deliberate inhalation from among a broad range of household and industrial chemical products with the intention of producing psychoactive effects. In addition to acute intoxication, prolonged inhalation of fluorinated compounds can cause skeletal fluorosis (SF). We report a young woman referred for hypophosphatasemia and carrying a heterozygous ALPL gene variant (c.457T>C, p.Trp153Arg) associated with hypophosphatasia, the heritable metabolic bone disease featuring impaired skeletal mineralization, who instead suffered from SF. Manifestations of her SF included recurrent articular pain, axial osteosclerosis, elevated bone mineral density, maxillary exostoses, and multifocal periarticular calcifications. SF was suspected when a long history was discovered of 'huffing' a computer cleaner containing 1,1-difluoroethane. Investigation revealed markedly elevated serum and urine levels of F-. Histopathology and imaging techniques including backscattered electron mode scanning electron microscopy, X-ray microtomography, energy dispersive and wavelength dispersive X-ray emission microanalysis, and polarized light microscopy revealed that her periarticular calcifications were dystrophic deposition of giant pseudo-crystals of francolite, a carbonate-rich fluorapatite. Identifying unusual circumstances of F- exposure is key for diagnosing non-endemic SF. Increased awareness of the disorder can be lifesaving.

Introduction Hypercalcemia in pregnancy is uncommon. Immediate evaluation and management is key to manage hypercalcemia in pregnancy to prevent maternal and fetal complications. Some common causes include primary hyperparathyroidism, vitamin D toxicity, and hyperthyroidism. An uncommon cause of hypercalcemia in pregnancy is small cell ovarian cancer, hypercalcemic type (SCCOHT). Case 26 year old woman, presented to the emergency department at 22 weeks of gestation with complaints of generalized weakness, fatigue, increased thirst, constipation, and intermittent right lower quadrant abdominal pain for 2 weeks. Past medical history was significant for polycystic ovarian syndrome. Labs revealed elevated albumin-corrected calcium: 17.5 mg/dl (8.7-10.5 mg/dl), low serum phosphorus: 2.1 mg/dl (2.7-4.5 mg/dl), low 25-OH vitamin D: 13 ng/ml (30-96 ng/ml), 1,25-OH Vitamin D: 44 pg/ml (20-79 pg/ml), and elevated PTHrP: 14 pmol/L (<2 pmol/L). The intact PTH was 12 pg/ml (9-77 pg/ml). TSH < 0.010 uIU/ml (0.4-4.0 uIU/ml) and free T4: 1.91 ng/dl (0.71-1.51 ng/dl). TSI & TPO levels were low. CA 125 was elevated: 135 U/ml (0-30 U/ml). Patient received IV hydration, IV furosemide, calcitonin, and pamidronate at the time of admission for management of hypercalcemia. MRI revealed large right adnexal mass measuring 19 cm; mostly solid but with cystic components. She underwent exploratory laparotomy with salpingo-oophorectomy. On post-op day 1 albumin corrected calcium decreased to 11.3 mg/dl. Repeat PTHrP on post-op day 3 decreased to 0.5 pmol/L. Pathology was notable for SCCOHT. At 27 weeks gestation, patient went into spontaneous labor and delivered. Following the delivery, she was started on chemotherapy with etoposide/cisplatin. After completion of one cycle of chemotherapy, her albumin corrected calcium level was 10.3 mg/dl. She was able to tolerate her first cycle of chemotherapy well and was in stable condition at the time of discharge. Discussion This case demonstrates an uncommon cause of hypercalcemia in pregnancy. Although rare (1% of all ovarian tumors), SCCOHT is an aggressive tumor with poor prognosis. SCCOHT should be considered as a differential in a young woman presenting with severe hypercalcemia. Majority of patients with SCCOHT have hypercalcemia, primarily mediated through the production of PTHrP, however our patient also had measurable calcitriol level possibly contributing to hypercalcemia. References Münstedt K, Estel R, Dreyer T, Kurata A, Benz A. Small Cell Ovarian Carcinomas - Characterisation of Two Rare Tumor Entities. Geburtshilfe Frauenheilkd. 2013;73(7):698-704.

The differential diagnosis of adult osteogenesis imperfecta (AOI) includes idiopathic osteoporosis, the Ehlers–Danlos syndrome (EDS), Marfan’s syndrome (MFS), including the Loeys–Dietz syndrome (LDS) subgroup and the hypermobility syndrome. The bone and extracellular matrix exhibit the key abnormality in each of these diseases. The phenotypic classification is based on the predominance of the tissue with the greatest matrix abnormality. AOI shows a predominance of bone abnormalities but also has joint and skin changes. EDS manifests changes in the joints and skin, MFS is associated with aortic aneurysms and eye problems, and LDS has vascular aneurysms, but each has a bone phenotype. Type I collagen is central to many of the disease processes, as the major structural protein of bone and connective tissue matrix. AOI and possibly some cases of idiopathic osteoporosis have quantitative defects of type I collagen; EDS has qualitative defects of type I collagen due to abnormal processing, collagen–collagen or collagen–noncollagenous protein interactions. TGF-beta modifies the matrix in MFS, LDS and possibly in idiopathic osteoporosis.

OBJECTIVE:Several studies have shown that patients with end-stage liver disease (ESLD) have lower bone mineral density (BMD) and a higher prevalence of osteoporosis compared to an age-matched population. Hyperinsulinemia and insulin resistance are typically associated with increased BMD. We hypothesized that patients with nonalcoholic steatohepatitis (NASH) and underlying insulin resistance may have higher BMD than patients with cirrhosis from other causes.METHODS:We performed a retrospective chart review of patients with ESLD who underwent liver transplant evaluation at Ochsner Clinic Foundation and had a BMD study as part of initial work up and compared BMD values of patients diagnosed with NASH to patients with cirrhosis due to other causes. Patients were categorized into 3 groups based on the etiology of their liver disease as NASH, alcoholic cirrhosis, or viral hepatitis C or B (HCV/HBV).RESULTS:A total of 63 patients met the study inclusion criteria, including 15 with NASH, 17 with alcoholic cirrhosis, and 31 with HCV/HBV. The overall prevalence rates of osteopenia and osteoporosis were 44% and 12%, respectively. BMD values were higher in the NASH group than the HCV/HBV group at lumbar spine, total hip, and femoral neck (P = .01, .03, and .02, respectively). There were no statistical differences in BMD values between NASH and alcoholic cirrhosis groups at any site.CONCLUSIONS:We found a high prevalence of low BMD among patients with ESLD awaiting liver transplantation. NASH patients had higher BMDs than HCV/HBV patients. The effects of NASH and insulin resistance on bone are complex and should be examined further.

A 69-year-old woman experienced subtrochanteric fracture of her right femur. She was walking into her house when she tripped and fell forward. She was seen at the emergency department, where she was diagnosed as having subtrochanteric femoral fracture. She underwent intramedullary rod placement.

PURPOSE:To determine whether a correlation between ABCC6 mutations and ocular phenotypic expressions exists.METHODS:In this study, 28 relatives of a consultand with known pseudoxanthoma elasticum were recruited for evaluation of the ocular manifestations of the disease, including peau d'orange appearance, angioid streaks, choroidal neovascular membranes, peripapillary atrophy, and retinal drusen. Comprehensive eye examinations were documented for all patients, who were then evaluated for the presence of known mutations in the aforementioned ABCC6 gene.RESULTS:Statistically significant correlations were noted between the gene and peau d'orange appearance (P  =  0.0016), angioid streaks (P < 0.0001), and choroidal neovascular membranes (P  =  0.0016).CONCLUSIONS:A statistically significant association was documented between the R39G mutation of the ABCC6 protein and 3 of 6 known manifestations of pseudoxanthoma elasticum. Although mutations of this gene are clearly associated with angioid streaks, the mechanism by which the transporter affects development of this pathology is speculative.

Reduced osteoblast function is a primary defect in glucocorticoid-induced osteoporosis (GIO), and is reflected by decreased biochemical markers of bone formation, such as serum osteocalcin (OC) and procollagen type I N-terminal propeptide (PINP). This analysis compared the effects of teriparatide and alendronate on OC and PINP in patients with GIO. In a double-blind study, women (N=159) and men (N=38) with GIO were randomized to either teriparatide 20 mug/day by subcutaneous injection or to alendronate 10 mg/day orally. OC and PINP were measured in fasting-state serum samples obtained at baseline and at 1, 6, 18, and 36 months. Baseline bone formation markers were below the reference interval (low) in 33% of patients for OC and in 4% of patients for PINP. On teriparatide therapy, the median OC and PINP levels increased by 92% and 108%, respectively, and this resulted in only 12% and 1% of patients being low at 6 months. On alendronate therapy, the median OC and PINP levels decreased by 40% and 53%, respectively, and this resulted in 68% and 34% of patients being low at 6 months. We conclude that bone formation as determined by surrogate markers was increased in teriparatide-treated patients with GIO and decreased in alendronate-treated patients with GIO.

The sub-segmental analysis of dual energy X-ray absorptiometry (DXA) scans from scoliotic vertebrae has established that there are differences in bone mass between the concave and convex sides of the vertebrae. Furthermore, these differences persisted in patients with low bone mass and were related to the geometry and applied loads, suggesting that this is a good model of bone adaptation in response to external stimuli. The goal of this study was to characterize the response of the human scoliotic spine to anti-resorptive treatments and estrogen withdrawal on the concave and convex sides of the spine. A total of 576 vertebrae (199 no treatment, 214 bisphosphonate, 69 estrogen and 94 estrogen withdrawal) were analyzed from 167 postmenopausal, Caucasian women. An analysis of variance (ANOVA) was used in conjunction with post-hoc Tukey tests to examine the effects of concavity, treatment group, and age. We found that the average change in BMD per year was greater than zero on the concave and convex sides with the exception of the estrogen withdrawal group. Discontinuing estrogen therapy caused patients to maintain bone mass on the concave side, but lose substantial bone density on the convex side. A differential response was also observed with respect to age. Patients younger than 60 exhibited a decrease in total BMD per year concomitant with a small degree of straightening, while those who were 60 or over demonstrated an increase in bone mass and a slight increase in the deformity. Based on these data, it is clear that the differences in BMD between the concave and convex sides of the vertebrae are not simply a result of the deformity, but more likely due to bone accretion. Further study is needed to elucidate the relationship between biomechanical forces and the adaptive response in the spine as a function of time.

OBJECTIVE:To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteoporosis subgroups. DESIGN:In this post hoc analysis, data were analyzed from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, enrolling postmenopausal women with low bone mass (N = 7705), and the Continuing Outcomes Relevant to Evista (CORE) trial, a follow-up to MORE enrolling 4011 MORE participants. Total follow-up was for up to 8 years. Women with a total hip bone mineral density (BMD) T-score < -1 to > -2.5 or T-score < or = -2.5 (referent, NHANES III database) were classified as having low bone mass or osteoporosis, respectively. Women with a pre-existing vertebral fracture were considered as having osteoporosis irrespective of BMD T-score. Analyses were performed for invasive breast cancers and invasive estrogen-receptor (ER) positive breast cancers. RESULTS:Women with low bone mass (N = 3829) had a twofold higher incidence of invasive ER-positive breast cancer than those with osteoporosis (N = 3836) (HR 2.13, 95% CI 1.12-4.03). The incidence of all invasive breast cancers did not differ significantly between the bone mass groups. The incidences of invasive and invasive ER-positive breast cancers were 65-78% lower in women assigned raloxifene versus placebo in both the low bone mass and osteoporosis groups (p < 0.05). CONCLUSIONS:In this post hoc analysis of postmenopausal women participating in MORE and CORE, bone mass was a predictor of invasive ER-positive breast cancer. Raloxifene treatment reduced the risk of invasive and invasive ER-positive breast cancers in women with low bone mass and those with osteoporosis. Since participants were older postmenopausal women with low bone mass, whether these findings can be generalized to other postmenopausal women is unclear.

The purpose of this post hoc analysis was to determine whether baseline concentrations or early changes in serum bone turnover markers were correlated with changes in bone mineral density (BMD) at 18 months in patients with glucocorticoid-induced osteoporosis (GIO) treated with teriparatide (n = 80; 20 mu g/day) or alendronate (n = 77; 10 mg/day). Bone markers included type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), bone alkaline phosphatase (bone ALP), and cross-linked C-telopeptide of type I collagen (S beta-CTX). The relationship between baseline and early changes in markers and the 18-month changes in lumbar spine (LS) and femoral neck (EN) BMD was evaluated using Spearman correlation analysis. In the teriparatide group, increases in LS and FN BMD at 18 months were not significantly correlated with baseline marker concentrations (P>0.05) but were correlated with the increases in PINP at 1 and 6 months (P<0.05). In the alendronate group, the increase in FN BMD at 18 months was positively correlated with baseline marker concentrations (P<0.05) and negatively correlated with change in PINP and S beta-CTX at 1 and 6 months. In addition, in the alendronate group, the increase in LS BMD was negatively correlated with change in S beta-CTX at 1 month (P<0.05). Increases in BMD at the spine and hip were independent of baseline bone turnover in the teriparatide group, while increases in hip BMD were dependent on baseline bone turnover in the alendronate group. With both therapies, early changes in some bone turnover markers were correlated with 18-month gains in BMD in patients with GIO. (C) 2009 Published by Elsevier Inc.

The dual purpose of this process paper is to describe the implementation of an intensive insulin infusion program against multiple barriers, despite the increasing evidence in the literature supporting glycemic control, and to report the glucose outcomes. Traditional hyperglycemic management has been done either by subcutaneous sliding scale or intravenous insulin infusions based on absolute glucose numbers. A review of the literature, with particular evidence within the cardiothoracic surgical (CTS) population, has shown significant deleterious effects of even mild hyperglycemia.Increasing evidence supporting prevention of hyperglycemia, along with an unsatisfactory review of current methods used in-house, prompted the initiation of a pilot program to improve current methods utilizing insulin therapy. A multidisciplinary committee was formed consisting of the director of the intensive care unit, a dietician, a nursing unit director, a charge nurse, an endocrinologist, and two endocrinology nurse practitioners with extensive experience in intensive insulin therapy, including continuous subcutaneous insulin infusion. A review of literature was performed to evaluate available data and intravenous insulin infusion algorithms used by published authors. The CTS population was chosen as well as the intensive care unit. Nursing barriers in particular were extensive, and the use of a velocity driven insulin protocol required didactic instruction as well as individual reinforcement. All education, algorithm development, and oversight of patients were primarily performed by the nurse practitioners with immediate endocrinologist availability if needed. A review of glucose results indicated a significant reduction in hyperglycemia with a decrease in hypoglycemia and facilitated transition to subcutaneous therapy when necessary.

A 63-year-old man complaining of painless hematuria was seen by his primary care physician. Prostatitis was diagnosed by history and urinalysis. A computed tomographic (CT) scan revealed a left adrenal mass measuring 3.8 cm in diameter (see Figure 1). No evidence of nephrolithiasis was seen, and he was referred to the Endocrinology Department for evaluation of the adrenal mass. Figure 1 Non-contrast CT demonstrating left adrenal mass. His medical history is significant for hypertension, coronary artery disease requiring stenting, carotid artery stenosis requiring angioplasty, and dyslipidemia. His surgical history includes a neck exploration after trauma, tonsillectomy, adenoidectomy, hemorrhoidectomy, and cataract surgery. He is a smoker and drinks alcohol occasionally. His father had a brain tumor and his mother had dementia, heart disease, and diabetes. He denied any family history of pituitary or adrenal disorders. His medications include clopidogrel, aspirin, simvastatin, atenolol, and valsartan. He denied vision changes, headaches, chest or abdominal pain, diaphoresis, polyuria, nocturia, paresthesias, or erectile dysfunction. He had no history of depression or fractures. His blood pressure was 165/80 mm Hg with a pulse of 70 beats per minute. Physical examination revealed an obese (229 lb, 71 in, body mass index = 30) man. There were no abdominal striae, moon facies, or supraclavicular fullness, and no skin abnormalities or bruising. The remainder of his physical examination was unremarkable. Upon review of his past laboratory studies, fasting hyperglycemia (118–165 mg/dL) was noted. A biochemical work-up (Table 1) was significant for abnormal 1 mg dexamethasone suppression, elevated urinary cortisol, and low adrenocorticotropic hormone (ACTH). A repeat 24-hr urine cortisol level remained elevated at 87 µg/24 h. Bone mineral density was normal. Table 1 Initial biochemical data. What Is The Diagnosis? Subclinical Cushing's syndrome (SCCS) was diagnosed because of the presence of an adrenal mass with abnormal 24-hr urinary-free cortisol, abnormal dexamethasone suppression, and comorbid hypertension, hyperglycemia, obesity, and cerebrovascular and coronary artery disease. A surgical consultation was obtained. The patient underwent a laparoscopic left adrenalectomy using an anterolateral transabdominal approach without complication. Perioperative steroids were not administered. His postoperative course was unremarkable, and he was discharged to home on postoperative day 1. Pathological analysis showed a 6-cm benign cortical adenoma. Postoperative laboratory studies showed normal 1 mg overnight dexamethasone suppression (1.2 µg/dL), resolution of his urinary hypercortisolism (43 µg/24 h) as well as normalization of his ACTH level (16 pg/mL). At 3-month follow-up, he has lost 5 pounds and has normal fasting blood glucose levels. His blood pressure has decreased to 130/65 mm Hg without medication changes.

Nearly one-third of all women and one-sixth of all men over age 65 have osteoporosis, and this condition is often accompanied by lumbar scoliosis. Previous work has shown that, in a group of postmenopausal women with scoliosis and osteoporosis, both the bone mineral content (BMC) and bone mineral density (BMD) were greater on the concave side than the convex side. The goal of this study was to examine the structure-function relationships in the spines of patients with low bone mass and scoliosis using a patient-specific biomechanical model. We compared the percent change in BMC and the percent change in BMD with axial force, Fa, shear force, Fs, moment, M, local curvature, θrel, and the patient’s age, A. We found that the percent change in BMC depended on the applied moment and the local curvature. The same dependence was observed for the percent change in BMD, but in this case, the shear force was also significantly inversely correlated. A population with femoral neck BMD with a T-score greater than –2.0 was similarly evaluated and yielded similar results. The percent change in BMD was related to M, θrel, A and negatively to the shear force. These results indicate that the osteoporotic spine is still able to respond to changes in the mechanical environment and provides a useful comparison between patients with osteoporosis and those with normal bone mass. In addition, this model may be a useful tool for the in vivo assessment of bone density changes in response to mechanical stimuli and drug treatments.