The potential role of mechanotransduction in the management of pediatric calvarial bone flap repair.

Pediatric patients suffering traumatic brain injuries may require a decompressive craniectomy to accommodate brain swelling by removing a portion of the skull. Once the brain swelling subsides, the preserved calvarial bone flap is ideally replaced as an autograft during a cranioplasty to restore protection of the brain, as it can reintegrate and grow with the patient during immature skeletal development. However, pediatric patients exhibit a high prevalence of calvarial bone flap resorption post-cranioplasty, causing functional and cosmetic morbidity. This review examines possible solutions for mitigating pediatric calvarial bone flap resorption by delineating methods of stimulating mechanosensitive cell populations with mechanical forces. Mechanotransduction plays a critical role in three main cell types involved with calvarial bone repair, including mesenchymal stem cells, osteoblasts, and dural cells, through mechanisms that could be exploited to promote osteogenesis. In particular, physiologically relevant mechanical forces, including substrate deformation, external forces, and ultrasound, can be used as tools to stimulate bone repair in both in vitro and in vivo systems. Ultimately, combating pediatric calvarial flap resorption may require a combinatorial approach using both cell therapy and bioengineering strategies.

Anatomical tibial component is related to more medial tibial stress shielding after total knee arthroplasty in Korean patients.

PURPOSE: This study aimed to investigate stress shielding of anatomical tibial components (ATCs) in comparison to conventional symmetric tibial components (STCs) in Korean patients which may be related to medial tibial bone loss. METHOD: 78 knees in 59 patients with ATCs (Persona™) and 74 knees in 58 patients with STCs (NexGen LPS-Flex™) were retrospectively reviewed. Radiographic parameters and clinical outcomes in both groups were compared. Logistic regression analysis was performed to identify risk factors for medial tibial bone loss. RESULTS: Medial tibial bone loss was significantly greater in the ATC group (1.6 ± 1.3 mm) than in the STC group (0.4 ± 0.8 mm) (p < 0.001). The ATC group showed a shorter distance between the distal metal tip and anteromedial cortex and higher invading into the sclerotic bone lesion (ISBL) than the STC group (p = 0.034 and p = 0.044, respectively). Multiple logistic regression analysis suggested ATC, a shorter distance to the anteromedial cortex, and the presence of ISBL as risk factors for medial tibial bone loss. The odds ratios of medial tibial bone loss according to type of prosthesis, distance to anteromedial cortex, and presence of ISBL were 6.25 (range 2.86-13.63, p < 0.001), 0.69 (range 0.51-0.93, p = 0.015), and 3.79 (range 1.56-9.21, p = 0.003), respectively. Notwithstanding, there was no difference in clinical outcomes between the two groups. CONCLUSION: In Korean patients, ATCs potentially causes greater medial tibial bone loss due to stress shielding than STCs. The design, however, does not yet appear to affect clinical outcomes at mid-term follow-up. LEVEL OF EVIDENCE: Retrospective cohort study, level III.

Double-Stranded RNA Is a Novel Molecular Target in Osteomyelitis Pathogenesis: A Translational Avian Model for Human Bacterial Chondronecrosis with Osteomyelitis.

Osteomyelitis remains a serious inflammatory bone disease that affects millions of individuals worldwide and for which there is no effective treatment. Despite scientific evidence that Staphylococcus bacteria are the most common causative species for human bacterial chondronecrosis with osteomyelitis (BCO), much remains to be understood about the underlying virulence mechanisms. Herein, we show increased levels of double-stranded RNA (dsRNA) in infected bone in a Staphylococcus-induced chicken BCO model and in human osteomyelitis samples. Administration of synthetic [poly(I:C)] or genetic (Alu) dsRNA induces human osteoblast cell death. Similarly, infection with Staphylococcus isolated from chicken BCO induces dsRNA accumulation and cell death in human osteoblast cell cultures. Both dsRNA administration and Staphylococcus infection activate NACHT, LRR and PYD domains-containing protein (NLRP)3 inflammasome and increase IL18 and IL1B gene expression in human osteoblasts. Pharmacologic inhibition with Ac-YVAD-cmk of caspase 1, a critical component of the NLRP3 inflammasome, prevents DICER1 dysregulation- and dsRNA-induced osteoblast cell death. NLRP3 inflammasome and its components are also activated in bone from BCO chickens and humans with osteomyelitis, compared with their healthy counterparts. These findings provide a rationale for the use of chicken BCO as a human-relevant spontaneous animal model for osteomyelitis and identify dsRNA as a new treatment target for this debilitating bone pathogenesis.

Biochemical bone turnover markers in hormonal disorders in adults: a narrative review.

BACKGROUND: Hormonal disorders are often associated with abnormal levels of bone turnover markers (BTMs). N-terminal propeptide of type I procollagen (PINP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) are the reference markers of bone formation and bone resorption, respectively. METHODS: A comprehensive literature search within the MEDLINE and Web of Science databases was performed. RESULTS: Acromegaly is associated with higher BTM levels, which decrease during the remission after treatment. Adult-onset growth hormone deficiency is often associated with decreased BTM levels. Growth hormone replacement therapy stimulates bone turnover and increases BTM levels. Hypothyroidism is characterized by general slowing of bone metabolism which is reflected by lower BTM levels. The replacement thyroid hormone therapy increases the bone turnover rate and BTM levels increase. Patients with thyroid cancer receive a suppressive dose of thyroid hormones and may have slightly elevated BTM levels. Patients with overt hyperthyroidism had higher BTM levels and anti-thyroid therapy induces a rapid decrease in the BTM levels. Patients with overt primary hyperparathyroidism have higher BTM levels, whereas those with asymptomatic and normocalcemic hyperparathyroidism usually have normal BTM levels. Hypoparathyroidism is characterized by slightly decreased BTM levels. Cushing's syndrome is characterized consistently by markedly decreased osteocalcin concentration, whereas data on other BTMs are discordant. CONCLUSIONS: BTMs help us to better understand mechanisms of the impact of hormonal disorders and their treatment on bone metabolism. However, it is unknown whether BTMs may be used to monitor the effect of their treatments on bone in the clinical practice.

Bone invasion-targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma.

Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity and lack of an effect on bone invasion are limitations of CDDP. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has been developed. The present study aimed to characterize the basis of the cytotoxicity of the novel platinum complex 3Pt in comparison with that of CDDP for oral squamous cell carcinoma. The ionic platinum complex was prepared to increase solubility and avoid platinum nephrotoxicity. Furthermore, 3Pt was designed to target bone hydroxyapatite and has germinal bisphosphonate moieties for drug delivery. In vitro antitumor activity was assayed in two oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of 3Pt, nude mice with OSC-19 were given 3Pt and CDDP. The in vitro growth-inhibitory effect of 3Pt was significantly less than that of CDDP. However, both 3Pt and CDDP showed equivalent antitumor effects in vivo. Mice injected with CDDP developed renal cell apoptosis; however, those injected with 3Pt were almost free of renal cell injury. In addition to similar in vivo antitumor effects, 3Pt decreased the volume of bone resorption compared to that with CDDP in a bone invasion model using OSC-19. In conclusion, considering the potential advantages in terms of noticeable antitumor activity on bone invasion and reduced nephrotoxicity, 3Pt represents a significant improvement in the development of bone-targeting platinum drugs.

Defining "early" cranioplasty to achieve lower complication rates of bone flap failure: resorption and infection.

BACKGROUND: Although cranioplasty (CP) is a frequently performed and simple procedure, complications are common, particularly bone flap resorption and infection. The timing of surgery is as an important contributory factor, but the optimal timing has not been clearly determined. OBJECTIVE: We retrospectively investigated bone flap resorption and surgical site infection after CP to determine the optimal timing of surgery for reduction of complications. METHODS: The study enrolled 126 patients who underwent decompressive craniectomy (DC) and subsequent CP. Patients with bone flap resorption or surgical site infection were analyzed as the "complication" group. Receiver operating characteristic curve analysis was performed and the Youden index was used to dichotomize "early CP" and "late CP" groups. Univariate and multivariate survival analyses were performed. RESULTS: The complication group included 42 patients. The Youden index was used to identify a cutoff value for the DC-CP interval of > 44 days, and this was used to define early (< 45 days) and late (≥ 45 days) CP. Late CP was a significant risk factor in univariate and multivariate Cox regression analyses. CONCLUSION: This study showed that early CP before 45 days after DC is associated with a lower rate of bone flap resorption and surgical site infection than late CP.

Relation of RANKL and OPG Levels with Bone Resorption in Patients with Acromegaly and Prolactinoma.

The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=-0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=-0.384, p=0.036 and r=-0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=-0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.

Vitamin D Deficiency and Its Influence on Bone Metabolism and Density in a Brazilian Population of Healthy Men.

Vitamin D supplementation is universal for postmenopausal women, but not for elderly men, in whom osteoporosis is also commonly neglected. This study aimed to evaluate vitamin D deficiency and its association with secondary hyperparathyroidism, bone resorption, and bone density in Brazilian men. A total of 120 men, 20-93 years, were evaluated for serum calcium, phosphorus, creatinine, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, biochemical markers of bone resorption (carboxy-terminal telopeptide, carboxy-terminal peptide of type I collagen), and bone mineral density (dual-energy X-ray absorptiometry). Glomerular filtration rate (GFR) below 30 mL/min/1.73 m2, chronic diseases, and medications affecting bone were the exclusion criteria. No participant reported previous low-impact fractures. In the overall population, 25(OH)D levels were below 30 ng/mL in 46.7%, and below 20 ng/mL in 27.6%. Among the 93 patients 50 years and older, 28 had osteoporosis. In those 70 years and older, the prevalence of vitamin D deficiency (42.1%), secondary hyperparathyroidism (46.4%), high bone resorption (39.6%), decreased GFR (39.2%), and osteoporosis (41.4%) was significantly higher than in the younger subjects (p < 0.005 for all comparisons). Serum parathyroid hormone increased with aging and declining GFR, but was not significantly associated with 25(OH)D or bone mineral density. There was a clear contribution of vitamin D deficiency to increased bone resorption and osteoporosis. Binary logistic regression model considering age, 25(OH)D, and bone resorption identified age ≥70 years as the main determinant of osteoporosis. Our data demonstrate a high prevalence of vitamin D deficiency in a male population living in Rio de Janeiro, and emphasize its participation on the pathogenesis of age-related bone loss. (Vitamin D deficiency and osteoporosis are common in elderly Brazilian men.).

Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

BACKGROUND: Mineral bone disease constitutes a common complication of post-kidney transplantation, leading to great disability. As there is no consensus on the optimal treatment for post-kidney transplant recipients (KTRs), we aimed to evaluate the efficacy and safety of bisphosphonate and its combined therapies. METHODS: We incorporated relevant trials to perform a network meta-analysis from direct and indirect comparisons. We searched PubMed, Embase and the CENTRAL and the reference lists of relevant articles up to August 1, 2017, for randomized controlled trials. The primary outcome was bone mineral density (BMD) change at the femoral neck and the lumbar spine. RESULTS: From a total of 864 citations, 18 randomized controlled trials with a total of 1200 participants were included. Five different regimens were considered. Bisphosphonate plus calcium revealed a significant gain in percent BMD change than calcium alone at the femoral neck (mean difference (MD), 5.83; 95% credible interval (CrI), 1.61 to 9.27). No significant difference was detected when restricting to absolute terms. At the lumbar spine, bisphosphonate and calcium with or without vitamin D analogs outperformed calcium solely (MD, 0.07; 95% CrI, 0.00 to 0.13; MD, 0.06; 95% CrI, 0.02 to 0.09). Compared to calcium with vitamin D analogs, adding bisphosphonate was associated with marked improvement (MD, 0.03; 95% CrI, 0.00 to 0.05). Considering percent terms, combination of bisphosphonate with calcium and vitamin D analogs showed greater beneficial effects than calcium alone or with either vitamin D analogs or calcitonin (MD, 10.51; 95% CrI, 5.92 to 15.34; MD, 5.48; 95% CrI, 2.57 to 8.42; MD, 6.39; 95% CrI, 0.55 to 12.89). Both bisphosphonate and vitamin D analogs combined with calcium displayed a notable improvement compared to calcium alone (MD, 7.24; 95% CrI, 3.73 to 10.69; MD, 5.02; 95% CrI, 1.20 to 8.84). CONCLUSIONS: Our study suggested that additional use of bisphosphonate was well-tolerated and more favorable in KTRs to improve BMD.

Idiopathic Condylar Resorption: A Survey and Review of the Literature.

PURPOSE: Idiopathic condylar resorption (ICR) is a relatively uncommon condition. Its diagnosis, etiology, and management options are controversial. Furthermore, it is difficult for 1 provider to collect a large cohort of ICR patients to develop a statistically significant study of these concerns. Therefore, the purpose of this study was to survey experienced temporomandibular joint (TMJ) surgeons who have managed ICR cases relative to these concerns, as well as review the management outcome literature. MATERIALS AND METHODS: SurveyMonkey (Palo Alto, CA) was used to canvas the 88 international TMJ surgeons on the TMJ Concepts (Ventura, CA) InterNetwork. This network connects a group of surgeons across the world who consistently perform TMJ surgery. The intent was to provide a global snapshot of the demographic, epidemiologic, diagnostic workup, and outcome data related to the management of ICR cases. RESULTS: The surveys from surgeons who did not respond to all 12 questions were not included in the results. After application of the exclusion criteria, complete data on a cohort of 100 patients were obtained and used for the study. A history of hormonal imbalance was reported in only 10% of patients; however, 42 of 94 women were reportedly taking birth control pills presumably affecting their menstrual cycles. The most common reason for consultation was Class II malocclusion (98% of patients). Treatment modalities varied and included orthodontics, orthotics, TMJ total joint replacement, orthognathic surgery, and disc repositioning. CONCLUSIONS: ICR management proved to be controversial among the surveyed surgeons. Multiple treatment options have been described in the literature, including medical management, orthognathic surgery only, TMJ and orthognathic surgery, and total joint prosthesis reconstruction. Long-term, controlled, multicenter clinical studies should be developed to evaluate outcomes of all nonsurgical and surgical management options for the ICR patient.

Decrease of Estradiol and Several Lifestyle Factors, but Not Helicobacter pylori Infection, Are Significant Risks for Osteopenia in Japanese Females.

BACKGROUND: The primary cause of osteoporosis in women is increased bone resorption and decreased bone density associated with reduced estrogen secretion. Several studies have demonstrated a relationship between Helicobacter pylori infection and osteoporosis regardless of estrogen levels. This study examined the relationship between H. pylori infection and osteopenia together with estrogen levels, calcium intake, and several lifestyle factors. METHODS: This study included 473 healthy women who underwent a general health examination. Multivariate analysis was performed, with age, body mass index (BMI), smoking habit, drinking habit, exercise habit, schooling duration, estradiol levels, birth history, calcium intake, schooling duration, smoking habit, drinking habit, exercise habit, and H. pylori infection as independent variables and the presence of osteopenia as a dependent variable. RESULTS: The adjusted OR for osteopenia with H. pylori infection was 0.95 (95% CI 0.55-1.63, p = 0.84). In contrast, osteopenia was significantly associated with age, low BMI, lesser schooling period, low estradiol levels, and low calcium intake. CONCLUSIONS: H. pylori infection was not a significant risk for osteopenia by the multivariate analysis, which included the primary confounding factors. Significant factors, such as estradiol and calcium intake, should be assessed together to study the association of H. pylori infection and osteopenia.

Does early exercise attenuate muscle atrophy or bone loss after spinal cord injury?

OBJECTIVES: To systematically identify and assess the evidence on the efficacy of exercise initiated early after traumatic spinal cord injury (SCI). METHODS: A comprehensive search (Any-2014) of eleven databases identified studies evaluating exercise interventions initiated within 12 weeks after SCI on muscle and bone loss in paralyzed limbs and comparing with standard care or immobilization. Two reviewers assessed methodological quality. One reviewer extracted data and critiqued results according to the Spinal Cord Injury Rehabilitation Evidence body of evidence framework. RESULTS: A total of 2811 titles were screened. Eleven studies were included: five randomized controlled trials, four cohort studies and two within-subject control studies. All provided level II evidence with a moderate risk of bias. Two studies found significant positive effects of high-load FES-resisted stance on physiological measures of muscle. Three reported positive effects of 3 months of Functional Electrical Stimulation (FES) on muscle size. Two studies found positive effects of 6-month body-weight supported treadmill training or FES on trabecular bone using pQCT. CONCLUSION: We found consistent evidence of positive effects of early exercise on muscle, possibly related to load intensity of the protocol. However, the heterogeneity of interventions and outcomes makes this determination speculative. Evidence for the effectiveness of early exercise on bone is scant and confined to measures of trabecular bone mineral density via pQCT. Transparent reporting of methods and variability of data, combined with standardization of valid and sensitive measures of muscle atrophy and bone loss, could facilitate future meta-analysis on this topic.

Bone mineral density in treated at a young age for differentiated thyroid cancer after Chernobyl female patients on TSH-suppressive therapy receiving or not Calcium-D3 supplementation.

Long-term management of patients with differentiated thyroid cancer (DTC) commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal health. Experience with female patients treated for DTC at a young age and who were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very limited to date. This cross-sectional study set out to investigate effects of Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and followed-up for an average of 10 years. BMD was found to be significantly higher in patients receiving Calcium-D3 medication than in patients not taking supplements. The level of ionized calcium was the strongest factor determining lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy ending in childbirth and HDL-cholesterol were associated with a weak adverse effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect BMD in women treated for DTC at young age, at least after 10 years of follow-up.

Imaging methods for quantifying glenoid and Hill-Sachs bone loss in traumatic instability of the shoulder: a scoping review.

BACKGROUND: Glenohumeral instability is a common problem following traumatic anterior shoulder dislocation. Two major risk factors of recurrent instability are glenoid and Hill-Sachs bone loss. Higher failure rates of arthroscopic Bankart repairs are associated with larger degrees of bone loss; therefore it is important to accurately and reliably quantify glenohumeral bone loss pre-operatively. This may be done with radiography, CT, or MRI; however no gold standard modality or method has been determined. A scoping review of the literature was performed to identify imaging methods for quantifying glenohumeral bone loss. METHODS: The scoping review was systematic in approach using a comprehensive search strategy and standardized study selection and evaluation. MEDLINE, EMBASE, Scopus, and Web of Science were searched. Initial selection included articles from January 2000 until July 2013, and was based on the review of titles and abstracts. Articles were carried forward if either reviewer thought that the study was appropriate. Final study selection was based on full text review based on pre-specified criteria. Consensus was reached for final article inclusion through discussion amongst the investigators. One reviewer extracted data while a second reviewer independently assessed data extraction for discrepancies. RESULTS: Forty-one studies evaluating glenoid and/or Hill-Sachs bone loss were included: 32 studies evaluated glenoid bone loss while 11 studies evaluated humeral head bone loss. Radiography was useful as a screening tool but not to quantify glenoid bone loss. CT was most accurate but necessitates radiation exposure. The Pico Method and Glenoid Index method were the most accurate and reliable methods for quantifying glenoid bone loss, particularly when using three-dimensional CT (3DCT). Radiography and CT have been used to quantify Hill-Sachs bone loss, but have not been studied as extensively as glenoid bone loss. CONCLUSIONS: Radiography can be used for screening patients for significant glenoid bone loss. CT imaging, using the Glenoid Index or Pico Method, has good evidence for accurate quantification of glenoid bone loss. There is limited evidence to guide imaging of Hill-Sachs bone loss. As a consensus has not been reached, further study will help to clarify the best imaging modality and method for quantifying glenohumeral bone loss.

What happens to the bone flap? Long-term outcome after reimplantation of cryoconserved bone flaps in a consecutive series of 92 patients.

BACKGROUND: Reimplantation of cryoconserved autologous bone flaps is a standard procedure after decompressive craniotomies. Aseptic necrosis and resorption are the most frequent complications of this procedure. At present there is no consensus regarding the definition of the relevant extent and indication for surgical revision. The objective of this retrospective analysis was to identify the incidence of bone flap resorption and the optimal duration of follow-up. METHODS: Between February 2009 and March 2012, 100 cryoconserved autologous bone flaps were reimplanted at the Department of Neurosurgery, Inselspital Bern. Three patients were not available for follow-up, and five patients died before follow-up. All patients underwent follow-up at 6 weeks and a second follow-up more than 12 months postoperatively. A clinical and CT-based score was developed for judgment of relevance and decision making for surgical revision. RESULTS: Mean follow-up period was 21.6 months postoperatively (range: 12 to 47 months); 48.9 % (45/92) of patients showed no signs of bone flap resorption, 20.7 % (19/92) showed minor resorption with no need for surgical revision, and 30.4 % (28/92) showed major resorption (in 4 % of these the bone flap was unstable or collapsed). CONCLUSIONS: Aseptic necrosis and resorption of reimplanted autologous bone flaps occurred more frequently in our series of patients than in most reports in the literature. Most cases were identified between 6 and 12 months postoperatively. Clinical observation or CT scans of patients with autologous bone flaps are recommended for at least 12 months. Patient-specific implants may be preferable to autologous bone flaps.

Ultrasonographic examination of rheumatoid arthritis patients who are free of physical synovitis: power Doppler subclinical synovitis is associated with bone erosion.

OBJECTIVE: The aim of this study was to investigate the characteristics of power Doppler (PD) subclinical synovitis in patients with RA who achieve clinical remission free from physical synovitis. METHODS: Twenty-nine RA patients were consecutively enrolled. All of the patients had achieved clinical remission [simplified disease activity index (SDAI) 3.3] for at least 6 months at the musculoskeletal ultrasound (MSKUS) examination. Additionally, none of the patients exhibited tender joints at 68 sites or swollen joints at 66 sites. MSKUS of bilateral wrist and finger joints, including the first to fifth MCP joints, the first IP joint and the second to fifth PIP joints, was performed and the findings obtained by grey scale (GS) and PD were graded on a semi-quantitative scale from 0 to 3. RESULTS: The median disease duration upon the introduction of DMARDs was 3 months and that at MSKUS examination was 21 months. The percentages of patients with PD synovitis in at least one joint were PD grade 1, 58.6%; PD grade 2, 31.0% and PD grade 3, 6.9%. The use of biological agents was low in patients with PD synovitis grade 2 (P < 0.05). The presence of US bone erosion was high by patient (P < 0.05) and by joint (P < 0.0001) with PD synovitis as compared with those without PD synovitis. However, no correlations were found between PD synovitis measures and serum biomarkers, including angiogenesis factors. CONCLUSION: PD subclinical synovitis correlates with several clinical characteristics, whereas conventional serum biomarkers are not useful for indicating the presence of subclinical PD synovitis.

Are asthmatic patients prone to bone loss?

BACKGROUND: Recent studies suggest an association between allergic diseases, including asthma, and lower vitamin D level, a well-known risk factor of osteoporosis. However, it is not yet clearly known whether patients with asthma are prone to bone loss. OBJECTIVE: To evaluate whether the occurrence of airway hyperresponsiveness (AHR) or asthma is related to significant changes in bone mineral density (BMD). METHODS: We retrospectively enrolled 7,034 patients who had undergone a health checkup program, including BMD tests and methacholine bronchial challenge tests, at the Seoul National University Hospital, Healthcare System Gangnam Center, from November 1, 2004 to April 30, 2011. Asthma was ascertained by self-reported medical diagnosis by a physician. Patients with a history of systemic corticosteroid medication use were excluded from the study. RESULTS: Among a total of 7,034 patients, 216 (3.1%) had a positive AHR test result, and 217 (3.1%) had a history of asthma. Lumbar spine and femur BMD of patients with AHR were significantly lower than those without AHR (-0.53 ± 1.50 vs -0.03 ± 1.49, -0.47 ± 0.97 vs -0.22 ± 0.99, respectively; P < .001 for both). After being adjusted for age, sex, body mass index, smoking status, postmenopausal state, and previous history of hormone replacement therapy, the proportion of patients with osteopenia or osteoporosis was much higher in the AHR-positive group than in the AHR-negative group (odds ratio, 1.715; 95% confidence interval, 1.252-2.349) and in the ever-asthma group than in the never-asthma group (odds ratio, 1.526; 95% confidence interval, 1.120-2.079). CONCLUSION: In the current study, AHR and asthma were related to clinically meaningful BMD decrease, although the causal relationship is unclear.

Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women.

PURPOSE: This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women. METHODS: Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D3, 5 µg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined. RESULTS: Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes. CONCLUSIONS: Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 µg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.

How I do it: managing bone health in patients with prostate cancer.

Urologists have two scenarios where they have to address bone loss or increased risk of fractures in men with prostate cancer. In the first setting, a patient who has been started on androgen deprivation therapy may develop cancer-treatment-induced bone loss. In the second setting, a patient's prostate cancer may have metastasized to the bone. This article describes six steps to manage bone health in patients diagnosed with prostate cancer in a community practice.