[Show abstract][Hide abstract] ABSTRACT: To identify variables that might influence health-related quality of life (HRQoL) in patients with and without a history of fracture, attending bone mineral density (BMD) assessment prior to diagnosis of osteoporosis.
This cross-sectional study included 312 newly referred postmenopausal women attending for a DXA scan, without a diagnosis of osteoporosis. Data were obtained from the medical history and the General Practitioner's letter. HRQoL, using SF36 was scored using published algorithms with reference to an age-related population from England. Regression analyses were used to determine relationships between HRQoL and BMD, age, fracture status and co-morbidities.
For all patients, the age-related physical component summary (PCS) and mental component summary (MCS) scores were 46 ± 10 and 47 ± 10, respectively. Controlling for confounding variables, low BMD at the femoral neck was associated with worse PCS scores (p = 0.010) and MCS scores (p = 0.034) in patients without fracture. In patients with a history of fracture, this relationship was less evident, and younger age (p < 0.00), increasing BMI (p = 0.016) and number of co-morbidities (p = 0.042) were associated with reductions in PCS scores.
Patients referred for BMD assessment before a diagnosis of osteoporosis had reduced PCS scores. In patients without fracture, low BMD contributed to this reduction in health-related quality of life. Low PCS scores in patients with fracture were seen only in younger subjects with osteoporosis.
Quality of Life Research 11/2014; 24(5). DOI:10.1007/s11136-014-0851-0 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rickets remains a significant health problem in West Africa (Jarrett et al. 2013). Some time ago, we (Oginni et al. 1996) and others (Thacher et al. 1997) followed up on earlier work that had described a form of rickets observed in adolescents in South Africa and in younger children in Nigeria that was refractive to vitamin D (Pettifor et al. 1981; Okonufua et al. 1991). Since then similar findings have been reported from around the world (Prentice 2013). In Nigeria, clinical studies have confirmed calcium-deficiency as the cause of this condition with radiological and biochemical healing evident after simple treatment with palatable oral calcium preparations (Oginni et al. 1999, 2004).This article is protected by copyright. All rights reserved.
Tropical Medicine & International Health 11/2014; 20(4). DOI:10.1111/tmi.12444 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dear Editor,Hjelle and colleagues  draw attention to the association of coeliac disease [CD] with fracture and discuss whether patients presenting with idiopathic osteoporosis should have serological testing for CD. Apart from the complications affecting the bone, they also draw attention to the possibility of increased morbidity and mortality in CD.In a service-based evaluation of serological testing for coeliac disease, women over 50 years, without a diagnosis of gluten sensitivity, referred for DXA scans underwent serological testing for coeliac disease if they fulfilled the following conditions: history of fracture or a BMI 2 (1 SD below the mean for referrals) plus a BMD below the value separating the second and third tertile of z score in patients known to have coeliac disease referred from the gastrointestinal department. This was −0.5 at the femoral neck (FN) (nHanes III) and −1.1 at L2–4 (LS) (Hologic database), both values equating to a T score of −2.5 at age 60–65
Osteoporosis International 06/2014; 25(9). DOI:10.1007/s00198-014-2771-9 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone mineral density at spine and hip is widely used to diagnose osteoporosis. Certain conditions cause changes in bone density at other sites, particularly in the lower limb, with fractures occurring in non-classical locations. Bone density changes at these sites would be of interest for diagnosis and treatment. We describe an application, based on an existing software option for Hologic scanners, which allows reproducible measurement of bone density at six lower limb sites (upper femur, mid-femur, lower femur; upper leg, mid-leg, lower leg). In 30 unselected subjects, referred for bone density, precision (CV%) measured on 2 occasions, separated by repositioning, ranged from 1.7% (mid-femur) to 4.5% at the lowest leg site. Intra-operator precision, measured by three operators on ten subjects on three occasions, was between 1.0% and 2.9%, whilst inter-operator precision was between 1.0% and 3.6%, according to region. These values compare well with those at the spine and upper femur, and in the literature. There was no evidence that this operator agreement improved between occasions 1 and 3. This technique promises to be useful for assessing bone changes at vulnerable sites in the lower limb, in diverse pathological states and in assessing response to treatment.
[Show abstract][Hide abstract] ABSTRACT: To review whether osteoporosis in the absence of vertebral fracture (VFX) affects health-related quality of life (HRQoL), a systematic search of the main literature databases for HRQoL in patients with osteoporosis without VFX was undertaken. This was undertaken. This identified 1,327 articles as potentially relevant to the review. After screening of abstracts and reviewing 168 articles in detail, 27 were considered relevant. HRQoL data were extracted and collated into tables and, where possible, were converted into normative scores and further analysed. Data relating to the associations between HRQoL and bone mineral density (BMD) were also collated. Of the 27 articles included, only 5 directly compared osteoporosis without VFX with a control group (BMD T-score > -1.0, without VFX). Extracted raw data from 21 articles demonstrated that patients with osteoporosis without VFX had clinically relevant reductions in role physical, general health, vitality, mental health domains and the mental component summary score, using SF36. Using Qualeffo-41, pain and physical function were worse in these patients. Also, HRQoL was related to upper femur, but not lumbar spine BMD. HRQoL data in patients with osteoporosis without VFX are limited and variable but suggest that HRQoL is adversely affected by osteoporosis in the absence of VFX. The association of lower BMD and worse HRQoL suggests that more attention should be paid to HRQoL in those without VFX. Future studies are needed to investigate HRQoL in patients with osteoporosis in the absence of fracture, controlling for co-morbidities and social and economic status.
Osteoporosis International 07/2012; 23(12). DOI:10.1007/s00198-012-2050-6 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bisphosphonates (BP) have been associated with osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). The prevalence of these side effects in intravenous (IV) BP-treated subjects is not well understood.
This audit aimed to delineate the prevalence of ONJ, thigh pain and AFF in patients having regular IV BP and its effect on bone mineral density (BMD). Design and
Patients attending for IV BP over a 3-month period completed a questionnaire about thigh pain and dental health. Data concerning BMD, treatment indication and treatment history were obtained from medical records.
There were 201 patients between 28 and 94 years (74.1% female) mostly on zoledronate (ZOL) (102) or pamidronate (PAM) (97). Osteoporosis (75.6%) and Paget's disease (16.5%) were the main indications for treatment; median length of IV BP was 4 years (range 0.25-25). One patient had ONJ (0.5%) while oral pain was reported by 6.5% and 12.7% noted tooth loosening. Twenty-seven subjects (13.4%) complained of current thigh pain. AFF occurred in four patients (2%), none of whom had idiopathic osteoporosis. At time of AFF, only one patient had a femoral neck T-score less than -2.5. All four had received pamidronate treatment; median 12.5 years (range 7-22). IV BP treatment significantly increased lumbar spine BMD but not femoral neck BMD.
Classical ONJ was rare (0.5%), although tooth loss was more frequent. Thigh pain was frequent while AFF occurred in 2.0% of subjects and was associated with long treatment periods and non-osteoporotic bone.
QJM: monthly journal of the Association of Physicians 06/2012; 105(10):965-71. DOI:10.1093/qjmed/hcs112 · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Routine DXA scanning in a 68-year-old asymptomatic man undergoing long-term bisphosphonate treatment for osteogenesis imperfecta showed unexplained loss of bone mineral density in two lumbar vertebrae. Subsequent radiographs revealed a 14-cm abdominal aortic aneurysm eroding the vertebrae. The importance of reviewing all the vertebrae in DXA scans is emphasized, and reasons for the absence of symptoms suggested.
Osteoporosis International 03/2012; 24(3). DOI:10.1007/s00198-012-1976-z · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the effect of 6 years of routine management on body composition, physical functioning, and quality of life, and their interrelationships, in men with idiopathic vertebral fracture.
Twenty men with idiopathic vertebral fracture (patients: mean ± SD age 58 ± 6 years) were age and height matched to 28 healthy controls with no known disease. The primary outcome was skeletal muscle mass (appendicular lean mass by dual x-ray absorptiometry) assessed at 2 visits (0 and 6 years). Physical functioning and quality of life domains were assessed by the Senior Fitness Test and Short Form 36 (SF-36) questionnaire at visit 2 only. Data were analyzed by repeated-measures analysis of variance, independent t-tests, and correlation.
At visit 1, appendicular lean mass was 9% lower in patients than controls. Although patients better maintained appendicular lean mass between visits (interaction P = 0.016), at visit 2 appendicular lean mass remained 5% lower in patients than controls. Furthermore, patients' appendicular lean mass change was correlated with femoral neck bone density change (r = 0.507, P = 0.023). Physical function tests were 13-27% lower in patients compared with controls (P = 0.056 to 0.003), as were SF-36 quality of life physical domains (13-26% lower; P = 0.028 to <0.001).
Despite an association between changes in muscle mass and bone density, routine management of men with idiopathic vertebral fracture does not address muscle loss. Combined with the observation of reduced physical functioning and quality of life, this study identifies novel targets for intervention in men with idiopathic vertebral fracture.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether the bone-resorption response to anastrozole differed according to initial patient age in postmenopausal women with breast cancer in a cross-sectional study. Second-morning void urines were collected for measurement of urinary cross-linked N-telopeptide of type I collagen (uNTx, corrected for creatinine and log-transformed) from postmenopausal women, 99 with breast cancer on anastrozole (ABC), 88 with newly diagnosed breast cancer (NDBC), and 137 community-dwelling healthy control (HC) women. Bone mineral density (BMD) was also measured at the lumbar spine (LS, L2-L4) and the femoral neck (FN) in the ABC group. uNTx (nanomole bone collagen equivalents/millimole creatinine) levels increased with age in HC subjects. In patients <70 years, anastrozole treatment led to a significant increase in uNTx compared with age-related HC subjects (1.74 vs. 1.55, P < 0.005). Patients >70 years showed no such increase compared to HC (1.72 vs. 1.69, nonsignificant); however, NDBC women >70 years had uNTx levels significantly lower than HC women (1.59 vs. 1.69, P < 0.05). There was no difference in uNTx levels above and below the age of 70 years in NDBC women (1.56 vs. 1.59, nonsignificant). ABC women were more likely to have a positive LS BMD z score than age-matched controls. Anastrozole treatment increases bone turnover more in younger postmenopausal women with breast cancer than in older women compared to healthy controls. Higher LS BMD in ABC patients may help protect against fracture.
Calcified Tissue International 03/2011; 88(3):223-30. DOI:10.1007/s00223-010-9452-2 · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop a 'close to patient' peripatetic intravenous service (PIVS) for delivery of specialist osteoporosis care in a community setting without increasing cost and with a reduced carbon footprint.
Cost and feasibility of a PIVS for intravenous (i.v.) bisphosphonate treatment were modelled using UK National Health Service costings and then tested in the field for 1 year. Average patient mileage to peripatetic sites was compared with mileage travelled if treated at the base hospital (current practice). The method of travel to hospital (current practice) or peripatetic sites (new study) was ascertained together with patients' preference for the new or the current system. Peripatetic sites were researched and those with suitable facilities selected. Data for fuel consumption were based on a usage of 1 litre per 14.5 km.
The main outcome measure was cost comparison between hospital and peripatetic services. Others included patient satisfaction, miles saved, method of travel to the clinic and changes in CO(2) emissions.
Cost per patient, including drugs, lies between pound557 and pound622 annually for 1000 and 500 patients, respectively which is cost-neutral compared with hospital attendance. PIVS was rated more convenient by 98% of patients. Hospital transport was significantly reduced and the total monthly saving of 2000 miles has reduced CO(2) emission by 6072 kg p.a. No medical emergency occurred in 410 infusions.
PIVS is cost neutral compared with a conventional service, leads to a better patient experience, a significant cutback in hospital transport costs and a reduction of the NHS carbon footprint. However not all drugs may be suitable for this service: the area served was rural with large distances and poor public transport and mileage savings may not accrue in urban areas. Insurance was not included in the calculation of costs.
Current Medical Research and Opinion 08/2010; 26(8):2033-9. DOI:10.1185/03007995.2010.497344 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alkaline phosphatase (ALP) is routinely used in the assessment of Paget's disease of bone (PDB); however, the individual bone ALP isoforms (B/I, B1, and B2) have not been investigated in this disorder.
Subjects comprised 37 patients (mean age 74 years) with symptomatic PDB confirmed by radiograph and stratified into high and low total ALP activity groups and 66 healthy individuals (mean age 64 years). Extracts of human cancellous and cortical bone tissues were also investigated. The bone ALP isoforms, measured by HPLC, were compared with two bone ALP immunoassays (Metra and Ostase), and the bone formation marker intact amino-terminal procollagen type I propeptide (iPINP).
All bone ALP isoforms were increased in high ALP activity PDB compared with the low ALP activity and control groups (p < 0.0001). The B2 isoform had the greater relative activity representing 36%, 50%, and 71%, of the total ALP activity in the control, low and high ALP activity groups, respectively. Compared with controls, B2 was increased in the low ALP activity PDB group (p < 0.05). ROC analysis showed a validity of approximately 80% for B2 to discriminate patients with PDB.
All bone ALP isoforms were increased in patients with high ALP activity PDB and the B2 isoform was even elevated in the low ALP activity PDB group. The bone ALP isoform B2 may be of use in the management of PDB but that has to be further elucidated in subsequent studies.
Scandinavian journal of clinical and laboratory investigation 02/2010; 70(2):128-35. DOI:10.3109/00365511003642527 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Management of osteoporosis is imperfect because patients may not start, persist or comply with treatment. This study was aimed to identify baseline variables associated with women failing to start, persist or comply with bisphosphonate treatment.
254 women >50 years old were selected 5 years after having a bone densitometry (bone mineral density (BMD)) diagnosis of osteoporosis. At the outset, information about osteoporosis was sent to the general practitioner (GP). Women were not under pressure at the outset to start or comply, and they and their GP were unaware that follow-up studies would take place. Patient survival was identified from the National Health Service Strategic Tracing Service, prescription data from GP records and baseline data from the initial questionnaire. Persistence was defined as at least one prescription issued per year and compliance as having a medicine possession ratio of >or=80% for each of 5 years.
38% failed to start treatment. Failure was associated with higher BMD Z score and residence in a nursing/residential home. Half of those starting and alive at 5 years persisted with treatment, whereas only 23% achieved a medicine possession ratio of >or=80%. Persistence was associated with a lower comorbidity index and compliance with a lower BMD Z score and a fall before starting treatment.
Treatment was low, especially in nursing/residential homes where known low treatment prevalence appears to be associated with non-initiation. The degree of depression of BMD (not just low BMD) was associated with better initiation and compliance. The association of falls with compliance suggests that fall clinics may be able to play a part in improving osteoporosis management.
Journal of epidemiology and community health 09/2009; 64(6):518-22. DOI:10.1136/jech.2008.084558 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A group of 5-day-old mice were injected intraperitoneally with (3-amino-1-hydroxypropylidine)-1,1-bisphosphonate (APD). Morphologic changes were observed in vitally stained osteoclasts on parietal bones 3 days later, and these were judged to be degenerative. At this time significantly increased numbers of nuclei per osteoclast and total numbers of osteoclast nuclei were observed. However, at 4 days after the injection of APD, the total numbers of osteoclasts were significantly reduced relative to controls. When parietal bones were maintained in culture, APD reduced osteoclast numbers and inhibited cell-mediated 45Ca2+ release. Exposure of bones to parathyroid hormone increased the number of osteoclasts counted 1 day later. This effect was not blocked by APD. Calcitonin prevented the reduction in osteoclast numbers due to APD in vitro. We conclude that APD has a direct effect on resorbing mouse osteoclasts.
Journal of Bone and Mineral Research 09/2009; 5(9):955-62. DOI:10.1002/jbmr.5650050909 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dickkopf-1 (Dkk-1) is a secreted inhibitor of Wnt signaling which in adults regulates bone turnover. Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1.
To see if increased Dkk-1 was detected in serum from patients with PDB.
Dkk-1 and total serum alkaline phosphatase activity (tsAP) were significantly elevated in sera from PDB patients. Patients with polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not significantly correlated.
Dkk-1 may be a useful biomarker of PDB and we speculate that Dkk-1 may play a central role in the etiology of PDB.
[Show abstract][Hide abstract] ABSTRACT: Osteoprotegerin (OPG) is a major regulator of osteoclastogenesis, bone resorption and vascular calcification. OPG is produced by various cell types including mesenchymally derived cells, in particular, osteoblastic cells. Here we show OPG production by osteoblastic cells was stimulated by platelet-derived growth factor (PDGF) in two human osteosarcoma cell lines (MG63, Saos-2), a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (hMSC) by 152%, 197%, 113% and 45% respectively over 24 h. OPG was measured in the cell culture medium by immunoassay. PDGF isoforms AA, BB and AB show similar stimulation of OPG production. Message for OPG was also increased similarly to the increased secretion into the culture medium. Using specific inhibitors of cell signalling we demonstrate that PDGF acts through the PDGF receptor, PKC, PI3K, ERK and P38 and not via NF-kB or JNK. The importance of PDGF in fracture healing suggests a role for OPG production in countering bone resorption during the early phase of this process.
[Show abstract][Hide abstract] ABSTRACT: Stroke increases the risk of hip fracture on the affected side. Although bone is lost by 1 year, rapidity of onset and relationship with immobility are uncertain. Using the bone resorption marker urinary cross-linked N telopeptide of type I collagen (uNTx), we examined bone resorption in the first 4 weeks after stroke, relating uNTx with bone density and mobility in subjects over 60 years. Two separate control groups acted as comparators, healthy (HC) and institutionalized (IC) controls, the latter to control for the effects of institutionalization. uNTx, urinary calcium (both related to creatinine and log-transformed), heel bone mineral density (BMD), Tinetti scores, and Barthel scores for prestroke function were measured. Log uNTx/Cr was lower in males compared with females, but this difference was not evident in stroke or IC subjects. Log uNTx/Cr was inversely related with BMD in females from both control groups and in male stroke subjects. Tinetti scores were divided into tertiles and were lower in stroke than IC subjects (P < 0.01). Log uNTx/Cr was similar in stroke and IC subjects in the lowest Tinetti tertile. Log uNTx/Cr was higher in stroke subjects of both sexes in the lowest tertile compared with the higher two tertiles combined (P < 0.05) and higher in all tertiles compared with HC subjects (P < 0.05). Subjects with a prestroke Barthel index of < or = 17 had higher log uNTx/Cr compared with HCs. Log uCa/Cr was higher only in male stroke patients. Bone resorption in stroke starts early, and measures to reduce this are merited.
Calcified Tissue International 02/2009; 84(2):118-25. DOI:10.1007/s00223-008-9203-9 · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Paget's disease is presenting at older ages, with a trend to monostotic disease, associated with lower serum total alkaline phosphatase (serum total ALP) levels. Sarcomatous transformation is a rare complication, which only half a century ago had a median age of presentation of less than 60 years. We have investigated whether sarcomatous change exhibits increasing age at presentation, whether the trend to monostotic Paget's disease exists, whether male predominance in sarcoma still continues and explored factors that might affect survival.
Notes of all patients from the Royal Orthopaedic Hospital, Birmingham primary malignant bone tumour registry were reviewed and all cases of Pagetic sarcoma since 1975 extracted. In addition to basic demographic data, mode of presentation, skeletal involvement by Paget's disease, history of treatment, presence of pulmonary metastases, serum total ALP levels and survival were obtained.
Unequivocal Pagetic sarcoma was identified in 32 patients (23 M, 9 F). Age at presentation was 73.8 years with no sex difference and with known pre-existing Paget's disease in 42%. Only 15% had received any specific Paget's disease treatment. Serum total ALP was not invariably markedly elevated (compared with non-sarcomatous disease) and was related to the number of skeletal sites, but not to the sarcoma histological subtype. Paget's disease was monostotic in 46%. Pagetic sarcoma fell from 23% to 8% of primary bone sarcoma referrals in patients aged over 50 years between the decades 1986-1995 and 1996-2005. Median survival remained poor at 0.66 years. Survival of greater than 2 years occurred in 4 patients, one of whom with a low grade Pagetic sarcoma being alive at 12 years follow up.
The proportion of Paget's disease patients with sarcoma has fallen steadily since Paget's original report and is now about 0.3%, the decline predating availability of effective therapy. Sarcoma is not necessarily associated with very high serum total ALP. It is present amongst polyostotic cases in the expected proportion suggesting that more widespread skeletal involvement by Paget's disease is not a significant risk factor for malignant transformation. Sarcoma is presenting later concurrent with the advancing age of non-malignant disease, but male predominance continues. Pagetic sarcoma is now rare, continues to have a poor prognosis and is often the presenting feature of the disease.
Bone 12/2008; 44(3):431-6. DOI:10.1016/j.bone.2008.11.002 · 3.97 Impact Factor