Quantitative Computed Tomography (QCT) of the Distal Forearm in Men Using a Spiral Whole-Body CT Scanner - Description of a Method and Reliability Assessment of the QCT Pro Software.

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.

Vitamin D receptor (VDR) gene polymorphism and osteoporosis risk in White British men.

In this study, VDR gene ApaI (rs7975232), BsmI (rs 1544410) and TaqI (rs731236) genotypes were compared in men with osteoporosis and male controls. Osteoporosis affects around 20% of all men and overall mortality in the first year after hip fracture is significantly higher in men than women, yet the genetic basis of osteoporosis is less well studied in males. This study consisted of White British males; 69 osteoporosis patients and 122 controls. BMDs at the lumbar spine (vertebrae L1-L4) and hip (femur neck) were measured by dual-energy X-ray absorptiometry (DEXA). The VDR gene ApaI, BsmI and TaqI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and association analysis was carried out at genotype and haplotype level. Our study suggests that TaqI polymorphism CC genotype frequency is lower in controls and further analysis of genotypes and BMD revealed a significant effect of TaqI polymorphism on Lumbar spine BMD. Two haplotypes (GCC and AAT) were associated with increased osteoporosis risk. In conclusion, VDR gene TaqI polymorphism in recessive mode had a significant effect on lumbar spine BMD within our study. Haplotypes GCC and AAT increase the risk of osteoporosis among White British males.

National Osteoporosis Society vitamin D guideline summary.

The National Osteoporosis Society (NOS) published its document, Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a practical clinical guideline on the management of vitamin D deficiency in adult patients with, or at risk of developing, bone disease. There has been no clear consensus in the UK on vitamin D deficiency its assessment and treatment, and clinical practice is inconsistent. This guideline is aimed at clinicians, including doctors, nurses and dieticians. It recommends the measurement of serum 25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical scenarios: bone diseases that may be improved with vitamin D treatment; bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate; musculoskeletal symptoms that could be attributed to vitamin D deficiency. The guideline also states that routine vitamin D testing is unnecessary where vitamin D supplementation with an oral antiresorptive treatment is already planned and sets the following serum 25OHD thresholds: <30 nmol/l is deficient; 30-50 nmol/l may be inadequate in some people; >50 nmol/l is sufficient for almost the whole population. For treatment, oral vitamin D3 is recommended with fixed loading doses of oral vitamin D3 followed by regular maintenance therapy when rapid correction of vitamin D deficiency is required, although loading doses are not necessary where correction of deficiency is less urgent or when co-prescribing with an oral antiresorptive agent. For monitoring, serum calcium (adjusted for albumin) should be checked 1 month after completing a loading regimen, or after starting vitamin D supplementation, in case primary hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected. The guideline focuses on bone health as, although there are numerous putative effects of vitamin D on immunity modulation, cancer prevention and the risks of cardiovascular disease and multiple sclerosis, there remains considerable debate about the evaluation of extraskeletal factors and optimal vitamin D status in these circumstances.

Epidemiology of lifetime fracture prevalence in England: a population study of adults aged 55 years and over.

BACKGROUND: fractures remain a substantial public health problem but epidemiological studies using survey data are sparse. This study explores the association between lifetime fracture prevalence and socio-demographic factors, health behaviours and health conditions. METHODS: fracture prevalence was calculated using a combined dataset of annual, nationally representative health surveys in England (2002-07) containing 24,725 adults aged 55 years and over. Odds of reporting any fracture was estimated separately for each gender using logistic regression. RESULTS: fracture prevalence was higher in men than women (49 and 40%, respectively). In men, factors having a significant independent association with fracture included being a former regular smoker [odds ratios, OR: 1.18 (1.06-1.31)], having a limiting long-standing illness [OR: 1.47 (1.31-1.66)] and consuming >8 units of alcohol on the heaviest drinking day in the past week [OR: 1.65 (1.37-1.98)]. In women, significant factors included being separated/divorced [OR: 1.30 (1.10-1.55)], having a 12-item General Health Questionnaire (GHQ-12) score of 4+ [OR: 1.59 (1.27-2.00)], consuming >6 units of alcohol in the past week [OR: 2.07 (1.28-3.35)] and being obese [OR: 1.25 (1.03-1.51)]. CONCLUSION: a range of socio-demographic, health behaviour and health conditions, known to increase the risk of chronic disease and premature death, are also associated with fracture occurrence, probably involving the aetiological pathways of poor bone health and fall-related trauma.

Population prevalence of ultrasound features of osteoarthritis in the hand, knee and hip at age 63 years: the Newcastle thousand families birth cohort.

BACKGROUND: Musculoskeletal ultrasound has been found to be more sensitive than radiographs in detecting osteophytes. Our objective was to measure the prevalence of features of osteoarthritis (OA), in the dominant hand, knees and hips using ultrasound, within the Newcastle Thousand Families birth cohort. METHODS: Participants were aged 61-63 (mean 63) years. Knee images were scored for presence of osteophytes and effusion. Hip images were scored for the presence of osteophytes and femoral head abnormality. The first carpometacarpal joint, metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of the index finger (dominant hand) were imaged for osteophytes. RESULTS: Among 311 participants, prevalence of osteophytes at the distal interphalangeal joint was 70% while it was 23%, 10% and 41% for index proximal interphalangeal and metacarpophalangeal and thumb base carpometacarpal joints respectively. Prevalence of knee osteophytes was 30%, hip OA was 41%. Prevalence of knee effusions was 24% (right) and 20% (left). Ultrasound evidence of generalised OA (48%) and isolated hand OA (31%) was common, compared to isolated hip or knee OA (5%) and both hip and knee OA (3%). CONCLUSION: This is the first study to assess prevalence of ultrasound features of OA in a population-based sample. The higher prevalence of hand/hip OA, when compared to previous radiographic studies, supports the hypothesis that ultrasound is more sensitive than radiography in detecting OA, particularly for osteophytes.

Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes.

A transcriptome analysis compared gene expression in human bone biopsy samples taken from lumbar spine and iliac crest, sites that experience high and low levels of mechanical stress, respectively. The analysis revealed that the zinc finger protein of cerebellum (Zic) family member transcription factor Zic1 was the most up-regulated gene in the lumbar spine (202-fold; P<10(-7)) in comparison with the iliac crest. Software analysis of differential gene expression in the biopsy samples identified the ciliary-related proteins PATCH1 and GLI-Kruppel family members Gli1 and Gli3 as part of a potential molecular network associated with Zic1. RT-PCR confirmed the expression of Zic1, Gli1, and Gli3 and other related key signaling mediators in osteoblastic cells and osteocytes in vitro. Zic1 was immunolocalized in the cytosol and nucleus of the murine osteocyte cell line MLO-Y4 and osteoblast-like cells MC3T3-E1 and in primary rat osteoblasts. MLO-Y4 cells subjected to prolonged oscillatory fluid flow showed increased localization of Zic1 in the nucleus with diminished levels in the cytosol, but no such changes were seen in MC3T3-E1 cells. A shear stress-induced increase in T-cell factor/lymphoid enhancer factor transcriptional activity was abolished by Zic1 gene silencing. These results suggest that Zic1, perhaps together with Gli1 and Gli3, may act as a link between mechanosensing and Wnt signaling. We conclude that Zic1, a neural developmental transcription factor, plays an important role in shear flow mechanotransduction in osteocytes.

Birth weight and early socio-economic disadvantage as predictors of sex hormones and sex hormone binding globulin in men at age 49-51 years.

OBJECTIVES: A number of associations have been shown between early growth and later sex hormone levels in women, but less is known about this relationship in men. This study investigated life-course predictors of sex hormones in men in the Newcastle Thousand Families birth cohort. METHODS: The Newcastle Thousand Families Study is a prospective study initiated in 1947. At age 49-51 years, 574 study members returned detailed self-completion questionnaires and 412 attended for clinical examination, including 172 men in whom blood samples were taken. Estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were measured. Free testosterone concentrations were also calculated. RESULTS: Social class at birth independently predicted FSH and LH, with higher levels with increasing socioeconomic disadvantage. SHBG was higher with increasing standardized birth weight and lower with increasing contemporary body mass index (BMI). BMI also predicted LH, SHBG, and testosterone. None of the variables included within this analysis were significant predictors of estradiol. No other associations were seen with any of the variables included from across the life-course. CONCLUSIONS: Our findings suggest that birth weight may be positively associated with SHBG and early socioeconomic status may be related to FSH and LH in men. These novel findings are independent of contemporary BMI. Given the links between sex hormones, SHBG and disease outcomes such as type II diabetes and osteoporosis, it is possible that sex hormones may play a mediating role in the associations between circumstances in early life and later risk of chronic disease.

Reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community.

BACKGROUND: Radiographs are the main outcome measure in epidemiological studies of osteoarthritis (OA). Ultrasound imaging has unique advantages in that it involves no ionising radiation, is easy to use and visualises soft tissue structures. Our objective was to measure the inter-rater reliability and validity of ultrasound imaging in the detection of features of knee OA. METHODS: Eighteen participants from a community cohort, had both knees scanned by two trained musculoskeletal sonographers, up to six weeks apart. Inter-rater reliability for osteophytes, effusion size and cartilage thickness was calculated by estimating Kappa (κ) and Intraclass correlation coefficients (ICC), as appropriate. A measure of construct validity was determined by estimating κ between the two imaging modalities in the detection of osteophytes. RESULTS: Reliability: κ for osteophyte presence was 0.77(right femur), 0.65(left femur) and 0.88 for both tibia. ICCs for effusion size were 0.70(right) and 0.85(left). Moderate to substantial agreement was found in cartilage thickness measurements. VALIDITY: For osteophytes, κ was moderate to excellent at 0.52(right) and 0.75(left). CONCLUSION: Substantial to excellent agreement was found between ultrasound observers for the presence of osteophytes and measurement of effusion size; it was moderate to substantial for femoral cartilage thickness. Moderate to substantial agreement was observed between ultrasound and radiographs for osteophyte presence.

The prevalence of osteoporosis in patients with severe hip and knee osteoarthritis awaiting joint arthroplasty.

BACKGROUND: the presence of osteoporosis in patients with hip and knee osteoarthritis (OA) has important implications for understanding disease progression and providing optimal surgical and medical management. OBJECTIVE: to determine the prevalence of osteoporosis among patients with osteoarthritis awaiting total knee arthroplasty or total hip arthroplasty aged between 65 and 80 years. DESIGN: cross-sectional observational study. SETTING: tertiary referral centre in Newcastle upon Tyne, UK. SUBJECTS: patients with osteoarthritis awaiting total knee hip arthroplasty aged between 65 and 80 years. METHODS: lumbar spine, bilateral femoral and forearm bone mineral density (BMD) measurements were obtained using dual-energy X-ray absorptiometry. RESULTS: the cohort consisted of 199 patients with a mean age of 72 years (SD 4), and 113 (57%) were women. The overall rate of osteoporosis at any site was 23% (46/199) and a further 43% (85/199) of patients would have been classified as osteopaenic according to World Health Organization criteria. Osteoporosis was more commonly detected in the forearm (14%) than the lumbar spine (8.5%) and proximal femur of the index side (8.2%). CONCLUSIONS: in summary, a significant proportion of patients with end-stage OA have osteoporosis but this diagnosis may be missed unless BMD measurements are performed at sites distant from joints affected by OA.

Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance.

BACKGROUND: Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration. RESULTS: The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing. CONCLUSIONS: This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders.

Randomized controlled trial of vitamin D supplementation in older people to optimize bone health.

Background: Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results. Objectives: This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry. Methods: A total of 379 adults aged ≥70 y (48% women; mean age: 75 y) from the northeast of England were randomly allocated to 1 of 3 doses of vitamin D3 [12,000 international units (IU), 24,000 IU, or 48,000 IU] given once a month. The primary outcome was change in BMD (ΔBMD) at the hip. Secondary endpoints comprised the dose effects on femoral neck BMD, falls, circulating calciotropic hormones, bone turnover markers, and adverse events. Results: The mean ± SD baseline plasma 25-hydroxyvitamin D [25(OH)D] concentration was 40.0 ± 20.1 nmol/L, which increased after 12 mo to a mean 25(OH)D of 55.9, 64.6, or 79.0 nmol/L for participants receiving a monthly dose of 12,000, 24,000, or 48,000 IU, respectively (P < 0.01 for difference). There was no between-group difference in ΔBMD. However, parathyroid hormone concentrations decreased in all 3 groups, with a significantly greater decrease in the 48,000-IU group compared with the 12,000-IU group (P < 0.01). There were no differences in any adverse events between groups, with 3 cases of hypercalcemia, none of nephrolithiasis, and 249 falls observed. Conclusions: There was no difference in change in BMD over 12 mo between the 3 doses of vitamin D, suggesting no effect of the intervention or a similar attenuation of the anticipated decrease in BMD over 12 mo. The treatment was safe and effective in increasing plasma 25(OH)D concentrations, with no dose-related adverse events. This trial was registered at the EU Clinical Trials Register (EudraCT 2011-004890-10) and the ISRCTN Registry (ISRCTN35648481).

Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline.

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn's disease.

AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn's disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.

Lifecourse study of bone health at age 49-51 years: the Newcastle thousand families cohort study.

OBJECTIVE: To quantify the direct and indirect effects of fetal (position in family, weight, and social class at birth), childhood (breast feeding, growth, infections, and social class in childhood, age at menarche), and adult life (social class, alcohol consumption, smoking, diet, reproductive history, exercise, hormone replacement therapy use), and adult size (height, weight) on bone health at age 49-51 years, as measured by bone mineral density, total scanned bone area of the hip and lumbar spine, and femoral neck shaft angle. DESIGN: Follow up study of the Newcastle thousand families birth cohort established in 1947. PARTICIPANTS: 171 men and 218 women who attended for dual energy x ray absorptiometry scanning. MAIN RESULTS: Fetal life explained around 6% of variation in adult bone mineral density for men, but accounted for less than 1% for women. Adult lifestyle, including effects mediated through adult weight accounted for over 10% of variation in density for men and around 6% for women. Almost half of variation in bone area for men was explained by early life. However, most of this was mediated through achieved adult height and weight. In women, less than 5% of variation in bone area was accounted for by early life, after adjusting for adult size. Most of the variation in each of the indicators for both sexes was contributed either directly or indirectly by adult lifestyle and achieved adult height and weight. CONCLUSIONS: The effect of fetal life on bone health in adulthood seems to be mediated through achieved adult height.

Self-report overestimates true height loss: implications for diagnosis of osteoporosis.

The Newcastle Thousand Families birth cohort dates from 1947; assessments have included height measurement at 22 and 50 years, when height loss was also assessed by self-report. A total of 388 attended for 50-year review of bone health, of whom 57 reported a median height loss of 2.5 cm, and 8 reported height loss of >3.5 cm. However, of 24 subjects for whom true height loss could be calculated, 7 had gained height, 9 were unchanged and only 8 had lost height since age 22 years. Self-report leads to over-reporting of height loss, and therefore should not be the sole measure of height loss. In clinical practice, objective confirmation of reported height loss should be undertaken, wherever possible, prior to further investigation.

Association between vertebral fracture and increased mortality in osteoporotic patients.

UNLABELLED: Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk. INTRODUCTION: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself. METHODS: We studied 677 women and men with osteoporosis, 28-88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score < -2.5 and -3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry. RESULTS: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health--including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age--the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI, 0.93, 6.23). CONCLUSIONS: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk.

Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study.

UNLABELLED: The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis. The incidence of vertebral fractures was significantly reduced by 46%. The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density, QUS, weight, and smoking. INTRODUCTION: This study aimed to determine if the bisphosphonate, clodronate (Bonefos), reduced the incidence of vertebral fractures in osteoporotic women. MATERIALS AND METHODS: Women fulfilling the WHO criteria for osteoporosis at the lumbar spine (T-score

Non-response to osteoporosis treatment.

There are now a number of effective treatments for osteoporosis, which increase bone mineral density (BMD) and decrease the risk of fractures. There is no clear consensus on the optimal method for assessing response to treatment in the individual patient. The goal of osteoporosis treatment is to prevent fractures after minimal trauma, but these are relatively uncommon events and cannot be totally avoided by the use of currently available therapies. Alternative methods of assessing response to treatment include serial measurement of BMD or the biochemical markers of bone turnover, but the observed changes may be misleading if they do not exceed the least significant change. The proportion of patients who fail to respond to osteoporosis treatments is difficult to quantify. Clinical trials show continuing bone loss in up to 15% of participants on hormone replacement therapy or bisphosphonates. Non-response to treatment is probably more common in clinical practice, but may be due to poor adherence to treatment recommendations. Other potential causes of an apparent failure to respond to treatment include the use of a weak antiresorptive agent, differences in bioavailability, low dietary calcium intake, vitamin D insufficiency and underlying causes of secondary osteoporosis. The management of patients who fail to respond to treatment includes confirmation that they are adhering to treatment and have an adequate dietary calcium intake and vitamin D status and excluding causes of secondary osteoporosis. Consideration should also be given to the addition of calcium and vitamin D supplementation and the use of alternative treatments for osteoporosis.