Loss of bone density and bone strength following premenopausal risk-reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study).

Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss. INTRODUCTION: This prospective study investigated bone health in women following premenopausal oophorectomy. METHODS: Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up. RESULTS: Mean age was 42.4 ± 2.6 years (n = 30) for the surgery group and 40.2 ± 6.3 years for controls (n = 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (kbend) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all p < 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and kbend (14.8%) were observed at 24 months (all p < 0.01). HT prevented losses in kbend, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (p = 0.01). CONCLUSION: This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.

Peripheral quantitative computed tomography (pQCT)-based finite element analysis provides enhanced diagnostic performance in identifying non-vertebral fracture patients compared with dual-energy X-ray absorptiometry.

Due to limitations of the predominant clinical method for diagnosing osteoporosis, an engineering model based on a dedicated CT scanner for bone density and structure was applied in fracture patients and controls. Improved diagnostic performance was observed, which supports its potential use in future research and clinical practice. INTRODUCTION: Dual-energy X-ray absorptiometry (DXA), the predominant clinical method for diagnosing osteoporosis, has limitations in identifying individuals with increased fracture risk. Peripheral quantitative computed tomography (pQCT) provides additional information and can be used to generate finite element (FE) models from which bone strength properties can be estimated. We investigated the ability of pQCT-FE properties to distinguish peripheral low-trauma fracture patients from healthy controls, by comparison with DXA and standard pQCT. METHODS: One hundred and eight fracture patients (77 females aged 67.7 ± 7.9 years, 31 males aged 69.7 ± 8.9 years) were recruited from a hospital fracture liaison service. One hundred and twenty healthy community controls (85 females aged 69.8 ± 8.5 years, 35 males aged 68.9 ± 7.2 years) were recruited. RESULTS: Significant differences between groups were observed in pQCT-FE properties, especially at the 4% tibia site. Fracture odds increased most per standard deviation decrease in pQCT-FE at this location [shear stiffness estimate, kshear, in females, OR = 10.34, 95% CI (1.91, 43.98); bending stiffness estimate, kbend, in males, OR = 8.32, 95% CI (4.15, 33.84)]. Area under the receiver operating characteristics curve (AUROC) was observed to be highest with pQCT-FE properties at 4% the tibia site. In females, this was 0.83 for the pQCT-FE variable kshear, compared with 0.72 for DXA total hip bone density (TH aBMD) and 0.76 for pQCT tibia trabecular density (Trb vBMD); in males, this was 0.81 for the pQCT-FE variable kbend at the 4% tibia site, compared with 0.62 for TH aBMD and 0.71 for Trb vBMD. There were significant differences in AUROC between DXA and pQCT-FE variables in both females (p = 0.02) and males (p = 0.03), while no difference was observed in AUROC between primary pQCT and pQCT-FE variables. CONCLUSIONS: pQCT-FE modeling can provide enhanced diagnostic performance compared with DXA and, given its moderate cost, may be useful in clinical settings.

Describing the resource utilisation and costs associated withvertebral fractures: the Build Better Bones with Exercise (B3E) Pilot Trial.

This analysis examined costs/resources of 141 women with vertebral fractures, randomised to a home exercise programme or control group. Total, mean costs and the incremental cost-effectiveness ratio (ICER) were calculated. Quality of life was collected. Cost drivers were caregiver time, medications and adverse events (AEs). Results show adding an exercise programme may reduce the risk of AEs. INTRODUCTION: This exploratory economic analysis examined the health resource utilisation and costs experienced by women with vertebral fractures, and explored the effects of home exercise on those costs. METHODS: Women ≥ 65 years with one or more X-ray-confirmed vertebral fractures were randomised 1:1 to a 12-month home exercise programme or equal attention control group. Clinical and health system resources were collected during monthly phone calls and daily diaries completed by participants. Intervention costs were included. Unit costs were applied to health system resources. Quality of life (QoL) information was collected via EQ-5D-5L at baseline, 6 and 12 months. RESULTS: One hundred and forty-one women were randomised. Overall total costs (CAD 2018) were $664,923 (intervention) and $614,033 (control), respectively. The top three cost drivers were caregiver time ($250,269 and $240,811), medications ($151,000 and $122,145) and AEs ($58,807 and $71,981). The mean cost per intervention participant of $9365 ± $9988 was higher compared with the mean cost per control participant of $8772 ± $9718. The mean EQ-5D index score was higher for the intervention participants (0.81 ± 0.11) compared with that of controls (0.79 ± 0.13). The differences in quality-adjusted life year (QALY) (0.02) and mean cost ($593) were used to calculate the ICER of $29,650. CONCLUSIONS: Women with osteoporosis with a previous fracture experience a number of resources and associated costs that impact their care and quality of life. Caregiver time, medications and AEs are the biggest cost drivers for this population. The next steps would be to expand this feasibility study with more participants, longer-term follow-up and more regional variability.

Build better bones with exercise (B3E pilot trial): results of a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in older women with vertebral fracture.

We pilot-tested a trial of home exercise on individuals with osteoporosis and spine fracture. Our target enrollment was met, though it took longer than expected. Participants stayed in the study and completed the exercise program with no safety concerns. Future trials should expand the inclusion criteria and consider other changes. PURPOSE: Osteoporotic fragility fractures create a substantial human and economic burden. There have been calls for a large randomized controlled trial examining the effect of exercise on fracture incidence. The B3E pilot trial was designed to evaluate the feasibility of a large trial examining the effects of home exercise on individuals at high risk of fracture. METHODS: Community-dwelling women ≥ 65 years with radiographically confirmed vertebral compression fractures were recruited at seven sites in Canada and Australia. We randomized participants in a 1:1 ratio to a 12-month home exercise program or equal attention control group, both delivered by a physiotherapist (PT). Participants received six PT home visits in addition to monthly phone calls from the PT and a blinded research assistant. The primary feasibility outcomes of the study were recruitment rate (20 per site in 1 year), retention rate (75% completion), and intervention adherence rate (60% of weeks meeting exercise goals). Secondary outcomes included falls, fractures and adverse events. RESULTS: One hundred forty-one participants were recruited; an average of 20 per site, though most sites took longer than anticipated. Retention and adherence met the criteria for success: 92% of participants completed the study; average adherence was 66%. The intervention group did not differ significantly in the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR 1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious adverse events in the intervention group and 12 in the control group. CONCLUSION: An RCT of home exercise in women with vertebral fractures is feasible but recruitment was a challenge. Suggestions are made for the conduct of future trials.

Determinants of bone mineral density in young Australian women; results from the Safe-D study.

The study aimed to explore determinants of bone parameters in young women. Most bone parameters were associated with height and lean mass. Bone parameters were not associated with vitamin D status. Future research should address whether interventions aimed at improving lean mass are beneficial to bone health in young women. INTRODUCTION: The implementation of prevention strategies during young adulthood may be crucial for osteoporosis prevention in later life, yet literature examining the determinants of bone health in premenopausal women is limited. We aimed to assess determinants of bone health, including serum 25-hydroxyvitamin D (25OHD), in females aged 16-25 years, living in Victoria, Australia, recruited through Facebook advertising. METHODS: Serum 25OHD was measured by liquid chromatography-tandem mass spectrometry and bone health was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) in 326 participants. RESULTS: Mean (± standard deviation) serum 25OHD was 69 ± 28 nmol/L and the prevalence of vitamin D deficiency (serum 25OHD <50 nmol/L) was 26%. Seven percent of participants (n = 23) reported taking a vitamin D supplement. Two percent of participants had low lumbar spine bone mineral density (Z-score <-2.0), 5% at the hip and 7% at the femoral neck. Serum 25OHD levels were not associated with DXA bone parameters, nor with pQCT bone parameters. Most bone parameters were positively associated with height and lean mass. CONCLUSION: Vitamin D status was not associated with bone health in young women in the current study. Our findings suggest that targeting other modifiable factors, such as lean body mass, is likely to be beneficial to bone health in young women. Longitudinal studies examining the association between vitamin D status and bone health in young women are necessary to confirm our findings. In addition, whether raising 25OHD levels is advantageous for young women's bone health is yet to be determined.

Maternal vitamin D and offspring trabecular bone score.

No studies have explored the relationship with maternal vitamin D (25(OH)D) in pregnancy and offspring trabecular bone score (TBS). Our data suggest that maternal 25(OH)D in early pregnancy, but not late, may be associated with offspring TBS in boys. These data act as hypothesis-generating findings for confirmation in larger, longer-term studies. INTRODUCTION: Trabecular bone score (TBS), a novel tool derived from dual-energy X-ray absorptiometry (DXA), reflects the microarchitecture of the vertebrae. It has been shown to predict fracture independent of standard DXA parameters in adult populations. Previously, we demonstrated that maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy is associated with offspring bone mineral content at age 11 years. However, associations with TBS have not been explored, thus we aimed to determine associations between maternal 25(OH)D and offspring TBS. METHODS: Data were collected from the Vitamin D in Pregnancy (VIP) study. Venous blood samples were taken at recruitment and at 28-32 weeks' gestation. Maternal 25(OH)D was measured by radioimmunoassay. Offspring (n = 195, n = 181 with complete measures) underwent spine DXA (GE Lunar), at age 11 years (median = 10.9 (IQR 10.9-11.4)). TBS was calculated using TBS iNsight software. RESULTS: Offspring of mothers with sufficient 25(OH)D levels (≥50 nmol/L) at recruitment had a higher TBS (1.363 vs. 1.340, p = 0.04). In multivariable linear regression models, after adjustment for child relative lean mass, sex and pubertal stage, a 10 nmol/L increase in maternal 25(OH)D was associated with a 0.005 (95% CI 0.000, 0.010, p = 0.04) increase in TBS. However when stratified by sex (p for interaction = 0.16), the association was significant in boys, but not girls. There were no associations with TBS and maternal 25(OH)D at 28-32 weeks. CONCLUSIONS: We speculate that maternal 25(OH)D in early pregnancy may be associated with TBS in offspring at age 11 in boys. These hypothesis-generating findings warrant confirmation with larger interventional and long-term follow-up studies.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

OBJECTIVES: Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. METHODS: Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. RESULTS: Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. CONCLUSION: These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Too Fit To Fracture: outcomes of a Delphi consensus process on physical activity and exercise recommendations for adults with osteoporosis with or without vertebral fractures.

UNLABELLED: An international consensus process resulted in exercise and physical activity recommendations for individuals with osteoporosis. Emphasis was placed on strength, balance, and postural alignment. Rather than providing generic restrictions, activity should be encouraged while considering impairments, fracture risk, activity history, and preference, and guidance on spine sparing techniques should be provided. INTRODUCTION: The objectives of this study were to establish expert consensus on key questions posed by patients or health care providers regarding recommended assessment domains to inform exercise prescription, therapeutic goals of exercise, and physical activity and exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. METHODS: The Too Fit To Fracture expert panel identified researchers and clinicians with expertise in exercise and osteoporosis and stakeholder groups. We delivered a modified online Delphi survey (two rounds) to establish consensus on assessment, exercise, and physical activities for three cases with varying risk (osteoporosis based on bone mineral density; 1 spine fracture and osteoporosis; multiple spine fractures, osteoporosis, hyperkyphosis, and pain). Duplicate content analyses of free text responses were performed. RESULTS: Response rates were 52% (39/75) and 69% (48/70) for each round. Key consensus points are the following: (a) Current physical activity guidelines are appropriate for individuals with osteoporosis without spine fracture, but not for those with spine fracture; (b) after spine fracture, physical activity of moderate intensity is preferred to vigorous; (c) daily balance training and endurance training for spinal extensor muscles are recommended for all; (d) providing guidance on spine-sparing techniques (e.g., hip hinge) during activities of daily living or leisure, considering impairments, fracture risk, activity history, and preference, is recommended rather than providing generic restrictions (e.g., lifting <10 lbs, no twisting), but for those with vertebral fracture, especially in the presence of pain, multiple fractures, or hyperkyphosis, the risks of many activities may outweigh the benefits-physical therapist consultation is recommended. Examples of spine-sparing techniques and exercise prescription elements are provided. CONCLUSIONS: Our recommendations guide health care providers on assessment, exercise prescription, and safe movement for individuals with osteoporosis.

Too Fit To Fracture: a consensus on future research priorities in osteoporosis and exercise.

UNLABELLED: An international consensus process identified the following research priorities in osteoporosis and exercise: study of exercise in high-risk cohorts, evaluation of multimodal interventions, research examining translation into practice and a goal to examine fracture outcomes. INTRODUCTION: To identify future research priorities related to exercise for people with osteoporosis with and without osteoporotic spine fracture via international consensus. METHODS: An international expert panel and representatives from Osteoporosis Canada led the process and identified opinion leaders or stakeholders to contribute. A focus group of four patient advocates identified quality of life, mobility, activities of daily living, falls, bone mineral density, and harms as outcomes important for decision-making. Seventy-five individuals were invited to participate in an online survey asking respondents to define future research priorities in the area of osteoporosis and exercise; the response rate was 57%. Fifty-five individuals from seven countries were invited to a half-day consensus meeting; 60% of invitees attended. The results of the online survey, knowledge synthesis activities, and results of the focus group were presented. Nominal group technique was used to come to consensus on research priorities. RESULTS: Research priorities included the study of exercise in high-risk cohorts (e.g., ≥ 65 years, low BMD, moderate/high risk of fracture, history of osteoporotic vertebral fractures, hyperkyphotic posture, functional impairments, or sedentary), the evaluation of multimodal interventions, research examining translation into practice, and a goal to examine fracture outcomes. The standardization of outcomes or protocols that could be evolved into large multicentre trials was discussed. CONCLUSIONS: The research priorities identified as part of the Too Fit To Fracture initiative can be used to inform the development of multicentre collaborations to evaluate and implement strategies for engaging individuals with osteoporosis in a safe and effective exercise.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

SUMMARY: Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. INTRODUCTION: Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. METHODS: In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. RESULTS: The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. CONCLUSION: Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Bone health and back pain: what do we know and where should we go?

Bone health is generally not considered in patients who present with chronic back pain. Nonetheless, bone health and back pain share common genetic and environmental correlates suggesting a co-dependence. Evidence exists for a relationship between back pain and impaired bone health. Here we present the evidence, theoretic framework and clinical relevance. Bone health and back pain are important determinants of musculoskeletal health. Back pain experienced in youth is a risk factor for future back pain, while suboptimal bone health during development increases the risk of skeletal fragility in later life. Generally, bone health is not considered in patients with chronic back pain who do not demonstrate other well-recognised bone health risk factors or associated conditions. Nonetheless, evidence suggests that back pain and impaired bone health share common environmental and genetic correlates, indicating that bone health ought to be considered in the context of back pain in otherwise healthy individuals. This review describes the likely mechanisms explaining the relationship between back pain and impaired bone health, evidence concerning the relationship and suggestions for future research. A narrative literature search was conducted using CINAHL, Medline, PubMed and Web of Science electronic databases. A history of back pain is associated with decreased bone mineral density in adults, yet this tends to be site-specific. No studies were identified examining this association in youth, yet the negative effects of childhood skeletal trauma and obesity on bone and spinal health provide indirect evidence for an association. Further research is required to clarify the impact of back pain on bone health at different lifespan stages using prospective cohort designs.

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis.

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

The transgenerational effect of maternal and paternal F1 low birth weight on bone health of second and third generation offspring.

Low birth weight programs diseases in adulthood, including adverse bone health. These diseases can have intergenerational and transgenerational origins, whereby transmission to subsequent generations occurs via both parental lines. Uteroplacental insufficiency surgery (Restricted) or sham surgery (Control) was performed on gestational day 18, in F0 Wistar-Kyoto rats. F1 Restricted males and females mated with breeders in order to generate F2 offspring of maternal and paternal lineages. F2 males and females were randomly selected for breeding to generate F3 offspring. F2 and F3 offspring did not have differences in birth weight irrespective of F1 low birth weight and parental line. Maternal line females had minor alterations to trabecular content and density at 6 months, these differences were not sustained at 12 months. Maternal line males had changes to trabecular content at 6 and 12 months; however, differences were no longer present at 16 months. Despite altered bone geometry at 12 and 16 months, bending strength remained unaffected at both ages. Bone health of paternal line females was not affected at 6 and 12 months. Paternal line males at 6 months had changes to trabecular and cortical content; cortical thickness, periosteal circumference and bending strength; however, these differences were no longer sustained at 12 and 16 months. Our data demonstrate that there is no transgenerational transmission of adverse bone health in F2 and F3 offspring, derived from low F1 birth weight females and males. Our results are novel, as bone health across generations and both parental lines has not been investigated in a model of low birth weight due to uteroplacental insufficiency.

Treatment of Paget's disease of bone: a survey of clinical practice in Australia.

Consensus guidelines for the treatment of Paget's disease of bone have been published, but it is not known how closely these reflect clinical practice. We conducted a multi-centre, stratified, retrospective review of case notes of 531 subjects treated for Paget's disease of bone between 2000 and 2005 in 29 Australian centres. The subjects received 1072 courses of bisphosphonate treatment (pamidronate 363, alendronate 324, risedronate 208, tiludronate 103, zoledronic acid 69, and etidronate 5). The most recent treatment received was oral therapy in 57% of patients (alendronate 29%, risedronate 24%, and tiludronate 4%) and intravenous in 43% (pamidronate 33%, and zoledronic acid 10%). For oral bisphosphonates, the percentages of courses which were at the recommended dosage and duration were: alendronate 33%, risedronate 60% and tiludronate 29%. Pamidronate was administered in a wide range of dosing schedules, most commonly 60 mg every 3 months (18%), 6 months (17%) or annually (12%), whereas zoledronic acid was mainly given as a 4 mg infusion (98%) as a single dose (52%) or annually (19%). Most clinicians reported taking into account symptoms, plasma alkaline phosphatase activity and anatomical location of disease in determining the need for treatment. Patient preference, intolerance of oral therapy and compliance were ranked highest in determining the choice between oral and intravenous therapy. We conclude that oral and intravenous bisphosphonate dosing regimens are both commonly used to treat Paget's disease of bone in Australia. Only a minority of courses of oral bisphosphonate treatment are at the recommended dosage and duration, and there is a lack of consensus on regimens for intravenous treatment.

Effects of strontium ranelate on spinal osteoarthritis progression.

OBJECTIVE: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment Of Peripheral OSteoporosis (TROPOS) trials performed on 1105 women with osteoporosis and concomitant radiological spinal OA at baseline, and for whom lumbar x-rays were available at baseline and over the 3-year treatment period. The presence and severity of osteophytes, disc space narrowing and sclerosis in the lumbar intervertebral spaces was graded according to a validated method, and an overall OA score was calculated for each intervertebral space. Back pain (measured on a five-point Likert scale only in SOTI) and health-related quality of life (SF-36 questionnaire) were assessed at baseline and after 3 years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. RESULTS: The proportion of patients with worsening overall spinal OA score was reduced by 42% in the strontium ranelate group, compared with placebo (RR, 0.58; 95% CI, 0.42 to 0.79; p = 0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (p = 0.03), while no significant difference was observed in terms of health-related quality of life between these patient groups. CONCLUSIONS: The results of this post-hoc analysis suggest that strontium ranelate could reduce the progression of the radiographic features of spinal OA and back pain in women with osteoporosis and prevalent spinal OA.

Omega-3 polyunsaturated fatty acid supplementation reduces hypertension in TGR(mRen-2)27 rats.

To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)-mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II activity) were maintained on a diet either deficient or sufficient in omega-3 PUFA from conception. Half the animals on each diet were treated with the angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed the omega-3 PUFA deficient diet were significantly more hypertensive than those fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body weight, body fat and plasma leptin were reduced by perindopril treatment but not affected by omega-3 PUFA supply. Given that the elevated blood pressure of the Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce hypertension via the renin-angiotensin system.

A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International.

OBJECTIVES: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. METHODS: This was a 12-month extension to the Fosamax Actonel Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study continued taking the same double-blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. RESULTS: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. CONCLUSIONS: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.