Reduce Fracture Incidence Research Articles

Role of vertebroplasty and balloon kyphoplasty in pathological fracture in myeloma: a narrative review

Up to 70% of multiple myeloma (MM) patients develop vertebral metastasis and subsequent pathological vertebral fractures (PVF). With contemporary systemic therapies, life expectancy of MM patients has improved drastically, and the need to manage pain and associated disability from PVF is increasingly a high priority. The aim of this review is to provide an updated comprehensive synthesis of evidence in the use of vertebral augmentation, including percutaneous vertebroplasty (PV) and balloon kyphoplasty (BKP), to treat MM-related PVF. A comprehensive multi-database search in accordance with PRISMA guidelines was performed up to 10 February 2021. Relevant English language articles were selected and critically reviewed. A total of 23 clinical studies have been included in the review. PV and BKP showed significant pain and functional improvements in terms of analgesia requirements, Cervical Spine Function Score, Eastern Cooperative Oncology Group scale, EQ-5D score, Karnofsky score, Neck Pain Disability Index, Oswestry Disability Index, Short form-36 (SF-36) questionnaire and VAS pain scale. Both procedures also reported promising radiographic outcomes in terms of vertebral height improvement, maintenance and restoration, as well as kyphotic deformity correction. Asymptomatic cement leakage was commonly reported. There was no significant difference between the two procedures. PV and BKP are safe and effective procedure that offers pain relief, reduction in pain associated disability and reduction of fracture incidence. Its minimally invasive approach is associated with minimal morbidity risk, making it a viable option in frail patients. Narrative review.

Bisphosphonate therapy after liver transplant improves bone mineral density and reduces fracture rates: an updated systematic review and meta-analysis.

To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis. Post-OLT fracture incidence was reported in nine studies (n=591). Total fracture incidence was 6.6% (CI: 3.4-12.4%) in bisphosphonate group and 19.1% (CI: 14.3-25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n=591; OR=0.037; CI: 0.18-0.77; P=0.008). Overall fractures were significantly lower in the oral group (n=263; OR=0.26; CI: 0.08-0.85; P=0.02) but not in the IV group (n=328; OR=0.45; CI: 0.16-1.26; P=0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.

What's new in bone disease and fractures in HIV?

People living with HIV (PWH) are at greater risk of low bone mineral density (BMD) and fractures compared to the general population. This narrative review summarises recent literature in the field, including the relative contribution of antiretroviral therapy and frailty to low BMD and fractures in PWH. The body of evidence indicating less impact on BMD from the use of tenofovir alafenamide compared to tenofovir disoproxil fumarate continues to grow, although this has not yet translated into data supporting a reduction in fracture incidence. Frailty, common in PWH, is associated with both fractures and alterations in renal-bone metabolism, but is an area that is understudied in relation to interventions to reduce fracture risk in PWH. Although a maturing field, research into interventions to reduce fracture incidence in PWH is lacking in both quantity and scope. Development of core outcome datasets for clinical trials along with trials focused on reducing or reversing frailty are required to guide improvements overall bone health outcomes in PWH.

Differential effects of abaloparatide and teriparatide on hip cortical volumetric BMD by DXA-based 3D modeling

SummaryIn postmenopausal osteoporotic women in ACTIVE, abaloparatide reduced fracture risk and increased areal bone mineral density (BMD) more than teriparatide at the hip and wrist. DXA-based 3D modeling showed significantly greater increases in hip cortical volumetric BMD with abaloparatide versus teriparatide. This may explain differences reported in aBMD by DXA.IntroductionIn ACTIVE, abaloparatide (ABL) increased bone mineral density (BMD) shown by dual-energy X-ray absorptiometry (DXA) while reducing fracture incidence in postmenopausal osteoporotic women. Changes in DXA BMD with ABL, 80 μg, were significantly greater than with open-label teriparatide (TPTD), 20 μg, at cortical sites including total hip, femoral neck, and 1/3 distal radius. The purpose of this study was to better understand the relative effects of ABL and TPTD on cortical and cancellous compartments in the proximal femur.MethodsHip DXA images from a subset of randomly selected patients in the ACTIVE trial (n = 250/arm) were retrospectively analyzed using three-dimensional modeling methods (3D-SHAPER software) to evaluate changes from baseline at months 6 and 18.ResultsSimilar significant increases in trabecular volumetric BMD (vBMD, + 9%) and cortical thickness (+ 1.5%) were observed with ABL and TPTD by 3D-DXA at 18 months. In contrast, only ABL significantly increased cortical vBMD versus baseline (+ 1.3%), and changes in both cortical vBMD and cortical surface BMD were significantly greater with ABL versus TPTD. In the TPTD group, changes in cortical vBMD were inversely correlated with changes in serum CTX (carboxy-terminal telopeptide of type I collagen) and PINP (procollagen type I N-terminal propeptide), suggesting that higher bone turnover may have attenuated cortical gains.ConclusionThese results suggest previously reported differences in areal BMD increases between ABL and TPTD may be due to differential effects on cortical vBMD. Further studies are warranted to investigate how these differences affect therapeutic impact on hip strength in postmenopausal women with osteoporosis.

Assessment of baseline bone turnover marker levels and response to risedronate treatment: Data from a Japanese phase III trial

BackgroundRisedronate increases bone mineral density (BMD) and reduces fracture risk, but treatment response may depend on the baseline state of bone turnover. Data regarding the selection of therapeutic drugs or the prediction of therapeutic effects with baseline levels of bone turnover markers (BTMs) as a reference are insufficient. We hypothesized that when the baseline levels of BTMs are higher, baseline BMD might be lower, changes in BMD at 12 months after risedronate treatment might be higher, and the reduction of fracture incidence might be greater. This study aimed to analyze the data of a phase III clinical trial of risedronate from Japan to investigate the relationships between baseline BTM levels and (1) baseline BMD, (2) changes in BMD at 12 months after the start of treatment, and (3) the incidence of new vertebral fractures. MethodsThis post-hoc analysis included 788 postmenopausal women with osteoporosis whose baseline BTM levels as well as baseline and endpoint BMDs were measured. Relationships between baseline BTM levels and BMD at baseline and 12 months after risedronate treatment and new vertebral fractures were examined. One-way analysis of variance, two-tailed Student's t-test, and Fisher's exact test were used to analyze the data. ResultsBaseline BMD showed a significant upward trend when baseline BTM levels were lower in the analysis by tertiles. New vertebral fractures tended to occur in patients with prevalent vertebral fractures, but the relationship between new fractures and BTM levels was not statistically significant. Regardless of BTM types, BMD percentage increments (%) and increments (g/cm2) with the 12-month treatment were high when pretreatment BTM levels were high (P < 0.0001), and a >5.0% increase in BMD was observed even if baseline BTM levels were within the normal range. A new vertebral fracture occurred in only six patients (0.77%), and there was not enough statistical power to clarify the relationship between baseline BTM levels and fracture risk reduction. ConclusionsWhen pretreatment BTM levels increased, baseline BMD tended to be lower and the increase in BMD with 12-month risedronate treatment was higher. However, BMD could still be increased even if the baseline BTM levels are within the normal range. Combined with available evidence, baseline BTMs may not have an important role in deciding the optimal therapy. To elucidate the relationship between baseline BTM levels and long-term fracture risk, it will be necessary to conduct more large-scale studies with a longer follow-up period in severe osteoporotic patients with a high fracture risk. Mini abstractWe evaluated the significance of baseline bone turnover markers in the response to risedronate treatment. The increase in the bone mineral density (BMD) with the 12-month treatment may be higher when the state of bone turnover at baseline is higher, and BMD could still be increased even if the baseline bone turnover is within the normal range.

Controversies in medicine: the role of calcium and vitamin D supplements in adults

Vitamin D is made in the skin when exposed to sunlight, so deficiency is usually the result of low sunlight exposure (eg, in frail older people and in individuals who are veiled). Calcium and/or vitamin D supplements have been used for the prevention and treatment of osteoporosis. The major trials in community-dwelling individuals have not demonstrated fracture prevention with either calcium, vitamin D, or their combination, but the results of a large study in vitamin D-deficient nursing home residents indicated a reduced fracture incidence. Trials show that vitamin D increases bone density when winter 25-hydroxyvitamin D levels are below 25-30nmol/L. However, assay expense and variability suggest that supplements are better targeted based on clinical status to frail older people and possibly to people with dark skin living at higher latitudes. A daily dose of 400-800 units (10-20μg) is usually adequate. Parenteral antiresorptive drugs can cause hypocalcaemia in severe vitamin D deficiency (<25nmol/L), which should therefore be corrected before treatment. Clinical trials have not demonstrated benefits of vitamin D on non-skeletal endpoints. Calcium supplements in healthy individuals are not needed, nor are they required in most people receiving treatment for osteoporosis, where they have not been shown to affect treatment efficacy. Calcium supplements cause constipation, bloating and kidney stones, and some evidence suggests they may cause a small increase in the risk of myocardial infarction. Low dose vitamin D is safe, but high doses result in more falls and fractures. Current evidence does not support the use of these supplements in healthy community-dwelling adults.

Unhealthy lifestyles are associated with the increased risk of low-energy fracture in Chinese men ≥ 50years, a population-based survey.

This study aims to investigate the incidence of low-energy fractures in men aged 50 years and older in China and to explore associated risk factors. All the relevant data were available from the China National Fracture Survey (CNFS), which was a cross-sectional survey carried out in eight Chinese provinces (municipalities) between January and May 2015. Through 2014, 76,687 men above 50 years participated in this study and 223 participants had low-energy fractures, indicating the incidence rate 290.8 (95%CI, 252.7-328.9)/100,000 men. Over 80% of the fractures occurred at home and on the common road. The fracture incidence rate presented a significant rising trend with advanced age (p = 0.039). Current smoking, alcohol overconsumption, insufficient sleep duration, and history of past fracture were identified as significant risk factors associated with low-energy fracture (p < 0.05). These results will assist the decisions regarding allocation of healthcare provision to populations of greatest need and aid the design and implementation of strategies to reduce fracture incidence. Accordingly, individuals should be encouraged to reduce alcohol consumption, immediately quit smoking, and get sufficient sleep, especially in those with a history of past fracture. In addition, primary preventives especially home prevention should be emphasized.

SAT-540 Bisphosphonates and Fracture Incidence in Young Adults

Introduction: Osteoporosis and its treatment have widely been studied in postmenopausal women. In contrast, limited evidence on osteoporosis and its treatment exists for the younger adults. Determining whether bisphosphonates truly help reduce fracture risk in the younger population can have profound effects on their quality of life and reduce overall healthcare costs. The objective of our study is to assess whether exposure to bisphosphonates reduces fracture incidence in a younger population (age 19-40 years) in a 5-year follow up period. Methods: This is a Retrospective cohort study where the Kaiser Permanente electronic health records were used to search for patients of age 19-40 with abnormal bone density (either Z-score < -2 or T-Score < -2.5). Age matched controls consisted of a population with no bisphosphonate exposure or exposure less than six months (n=358). The treatment cohort consisted of those started on bisphosphonate therapy for a minimum of 6 months within 4 years of their first Dual-energy X-ray absorptiometry (DXA) (n=64). We compared the subsequent incidence of fracture of both groups as well as time to fracture to see if there was a significant difference between the two groups. over the 5-year follow up period. Comparisons were analyzed with chi-square for categorical variables and Wilcoxon rank sum test for continuous variables. Results: 422 patients were identified with abnormal bone density. 64 were found to have bisphosphonates exposure. Fracture occurred in 32 (9.8%) patients in the control group. 6 (10.3%) patients were found to have fracture in the treatment group. T-score were noted to be -2.3±0.80 and -2.53±0.58 for the control and treatment group respectively. Using multivariable logistic regression, no significant differences were found between groups in total fractures (Hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.26-6.26)). Similarly, no correlation was noted between the length of bisphosphonate therapy and fracture incidence (Odds ratio (OR) 0.996 (95% CI 0.966-1.026)). Conclusion: Several studies have shown the reduction of fracture incidence with the use of bisphosphonates in postmenopausal women. Our study investigated their effects in young adults. No significant differences in total fracture incidence were noted between groups. Although lower T-scores were noted in the treatment group, we didn't find a correlation between T-score and fracture risk. This finding may suggest that there is a variation in the pathophysiology of low bone density in young adults such that they don't have bone resorption or true osteoporosis. This could be one of the reasons why standard therapy for osteoporosis may not have shown benefits in our treatment group. Further research into the pathophysiology of low bone density in young adults and what specific etiologies would benefit from antiresorptive therapy may be needed for more definitive conclusions.

Circulating serum vitamin D levels and total body bone mineral density: A Mendelian randomization study.

Until recently, randomized controlled trials have not demonstrated convincing evidence that vitamin D, or vitamin D in combination with calcium supplementation could improve bone mineral density (BMD), osteoporosis and fracture. It remains unclear whether vitamin D levels are causally associated with total body BMD. Here, we performed a Mendelian randomization study to investigate the association of vitamin D levels with total body BMD using a large‐scale vitamin D genome‐wide association study (GWAS) dataset (including 79 366 individuals) and a large‐scale total body BMD GWAS dataset (including 66,628 individuals). We selected three Mendelian randomization methods including inverse‐variance weighted meta‐analysis (IVW), weighted median regression and MR‐Egger regression. All these three methods did not show statistically significant association of genetically increased vitamin D levels with total body BMD. Importantly, our findings are consistent with recent randomized clinical trials and Mendelian randomization study. In summary, we provide genetic evidence that increased vitamin D levels could not improve BMD in the general population. Hence, vitamin D supplementation alone may not be associated with reduced fracture incidence among community‐dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture.

First-in-Human Study of Bone Pathologies Using Low-Cost and Compact Dual-Wavelength Photoacoustic System

Osteoporosis affects one-third of the elderly population worldwide with associated health care costs amounting to tens of billions of dollars annually. Identifying and treating the population at risk of fracture, but had not yet suffered from a fracture, can substantially reduce fracture incidence. Unfortunately, molecular changes in the bone, which are of great importance for early diagnosis, are not detected by current low-cost diagnostic methods. To address this issue, presented here is a clinically translatable, dual-modality multispectral photoacoustic system. Ex vivo experiments demonstrated sensitivity to the molecular changes. Specifically, the system enabled a quantitative measurement of the marrow's blood/fat ratio. First-in-human demonstration on healthy human volunteers showed the repeatability and accuracy of the photoacoustic method and its potential for early diagnosis of bone pathologies.

Advances in osteoporosis from 1970 to 2018.

In 1970, there were no drugs under study for osteoporosis. Estrogen was used, but little was known about the correct dose for preventing bone loss. At that time, fractures were not even recognized as a disease, but regarded as part of normal aging. From 1970 to this year (2018), there have been extensive advances in the osteoporosis field ranging from fracture epidemiology to the remarkable invention of bone density measurements. There have been major advances in therapeutic options available for patients for prevention and treatment of osteoporosis. In parallel, the advances in the laboratory helped elucidate the process of bone remodeling, not only at the macroscopic level but also at the cellular level. This led to rapid advances in translational research from cellular biology to new therapies exemplified by the development of monoclonal antibodies for osteoporosis. Further understanding of the signaling pathways in bone cells will lead to new small molecules made for osteoporosis treatment, perhaps causing less adverse events. University-based research throughout the world has been a leader in most of these advances, and Pharma support for phase 1 to 4 studies helped bring these discoveries to patients. In the osteoporosis field alone, one sees the tremendous value of grant support for university research by National funding agencies such as the National Institute of Health in this country and similar agencies in other countries. There are clinical challenges that have to be solved with long-term compliance with osteoporosis medication if we want to reduce fracture incidence in the long term.

Novel mutations in BMP1 induce a rare type of osteogenesis imperfecta

BackgroundOsteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. OI patients of autosomal recessive inheritance are extremely rare, of which OI type XIII is attributable to mutation in BMP1 gene. Case reportHere, we detect the pathogenic mutations and analyze their relation to the phenotypes in a Chinese family with OI using next-generation sequencing (NGS) and Sanger sequencing. We also evaluate the efficacy of alendronate treatment in the patient with OI type XIII. The clinical phenotypes of the patient included recurrent fractures, muscle weakness, bone deformity, macrocephaly and elbow contractures, but no blue sclera or dentinogenesis imperfecta. High-resolution peripheral quantitative computed tomography revealed high bone mineral density and bone volume, but reduced trabecular numbers, increased porosity and comprised strength in this patient. Novel heterozygous mutations of c.1324G > T (p.Asp442Tyr) and c.148 + 1G > A in BMP1 gene were found in the proband, which would affect the CUB2 domain and the prodomain of mutant proteins. The parents were heterozygous carriers for the two mutations respectively, but with normal phenotype. ConclusionsWe report for the first time that the novel pathogenic mutations in BMP1 can lead to the extremely rare OI type XIII, which exhibit unique characters of high bone mass, but with impaired bone microstructure and comprised bone strength. Alendronate is beneficial in increasing bone mineral density and decreasing bone resorption biomarkers, but concerns still remain whether it can reduce fracture incidence in this rare type of OI.

Continuing Relief of Pain with Long Term Treatment for Osteoporosis with Intravenous Pamidronate

Purpose: Bisphosphonates are valuable in reducing the incidence of fracture. Side effects limit persistence with oral therapy and long term studies of pain relief are difficult to pursue. Intravenous bisphosphonates offer an alternative treatment to oral bisphosphonates and are tolerated over a longer period. The use of Pamidronate, an intravenously administered bisphosphonate, to benefit pain and reduce fracture incidence in the long term has not been extensively investigated. The study aimed to investigate the effect of Pamidronate on pain, vertebral fracture incidence and Bone Mineral Density over 6 or more years.Methods: Patients were offered intravenous Pamidronate if oral treatment with bisphosphonates or Hormone replacement therapy had failed due to side effects, fractures continued on oral treatment or oesophageal reflux led to cessation of oral treatment. Pain was assessed using the Nottingham health profile; radiographs were used to evaluate vertebral fracture and DXA measured bone mineral density.Results: The primary outcome was the pain domain. Median patient follow up was 9 years. Pain had improved significantly (p = 0.03) and in 68% pain had either improved or remained unchanged. Vertebral fractures occurred in 14% of patients in the first 3 years, 9.5% in years 4-6, but increased in years 7-9 to 27%. Bone mineral density increased in the lumbar spine (p &lt; 0.001) but not at the femoral neck.Conclusions: Pamidronate had a beneficial effect on pain over the period of the study. Vertebral fracture incidence increased after 6 years of Pamidronate, although spine BMD increased significantly.

Do reductions in out-of-pocket expenses for dual energy X-ray absorptiometry scans translate to reduced fracture incidence amongst older Australians? A population-based study.

In 2007, Medicare Australia revised reimbursement guidelines whereby individuals aged 70years and over received reduced out-of-pocket expenses for dual energy X-ray absorptiometry (DXA) scans. The current study aims to determine whether fracture incidence in the elderly has changed since the revision of reimbursement guidelines. Keyword searches of the two major radiological centres servicing the Barwon Statistical Division (BSD) were used to identify incident fractures for residents aged 75years and over for 2006 and 2012. Pathological fractures were excluded. Fracture incidence by age strata (75-79years, 80-84years and 85+ years) were calculated using population-specific data from the Australian Bureau of Statistics (2006 and 2012). Standardised fracture ratios were calculated for men and women. In total, 996 fracture events were identified for BSD residents during 2006 and 1260 identified in 2012. The standardised fracture ratios between 2006 and 2012 were 1.12 (95%CI 1.11, 1.25) for men and 1.08 (95%CI 1.11, 1.16) for women. The change in reimbursement guidelines appears to have had little impact on reducing fracture incidence during this time frame for elderly men and women, in fact, fracture rates increased. Future research should investigate osteoporosis management following DXA over a longer time frame.

Real-world effectiveness of osteoporosis therapies for fracture reduction in post-menopausal women

SummaryStudies examining real-world effectiveness of osteoporosis therapies are beset by limitations due to confounding by indication. By evaluating longitudinal changes in fracture incidence, we demonstrated that osteoporosis therapies are effective in reducing fracture risk in real-world practice settings.IntroductionOsteoporosis therapies have been shown to reduce incidence of vertebral and non-vertebral fractures in placebo-controlled randomized clinical trials. However, information on the real-world effectiveness of these therapies is limited.MethodsWe examined fracture risk reduction in older, post-menopausal women treated with osteoporosis therapies. Using Medicare claims, we identified 1,278,296 women age ≥ 65 years treated with zoledronic acid, oral bisphosphonates, denosumab, teriparatide, or raloxifene. Fracture incidence rates before and after treatment initiation were described to understand patients’ fracture risk profile, and fracture reduction effectiveness of each therapy was evaluated as a longitudinal change in incidence rates.ResultsFracture incidence rates increased during the period leading up to treatment initiation and were highest in the 3-month period most proximal to treatment initiation. Fracture incidence rates following treatment initiation were significantly lower than before treatment initiation. Compared with the 12-month pre-index period, there were reductions in clinical vertebral fractures for denosumab (45%; 95% confidence interval [CI] 39–51%), zoledronic acid (50%; 95% CI 47–52%), oral bisphosphonates (24%; 95% CI 22–26%), and teriparatide (72%; 95% CI 69–75%) during the subsequent 12 months. Relative to the first 3 months after initiation, clinical vertebral fractures were reduced for denosumab (51%; 95% CI 42–59%), zoledronic acid (25%; 95% CI 17–32%), oral bisphosphonates (23%; 95% CI 20–26%), and teriparatide (64%; 95% CI 58–69%) during the subsequent 12 months.ConclusionIn summary, reductions in fracture incidence over time were observed in cohorts of patients treated with osteoporosis therapies.

Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A Narrative Review.

ABSTRACTRecombinant human parathyroid hormone (PTH) is the key anabolic agent used for preventing fracture in postmenopausal women with osteoporosis. In bone metabolism, PTH signaling is mediated through a G protein–coupled receptor that affects various post‐receptor signaling pathways. Results of preclinical and clinical studies have shown that PTH improves both the structure and strength of bone tissue. Once daily subcutaneous injection of the PTH fragment, teriparatide (PTH [1‐34]), is the most commonly recommended formulation and dosing strategy in clinical practice. However, other dosing intervals, formulations, and routes have been investigated in preclinical and clinical studies. In particular, once‐weekly and cyclical administration have been investigated mainly as a means of reducing the high direct costs of treatment. In preclinical studies, bone formation/resorption markers, bone mineral density measurements, and histomorphometric parameters improved with both once‐daily and once‐weekly administration. However, the magnitude and duration of such improvements were generally greater with once‐daily PTH administration. In clinical studies, reductions in fracture incidence were also noted with both once‐daily and once‐weekly PTH administration, although improvements in nonvertebral fractures are less evident with once‐weekly administration. This narrative review details the differences between PTH formulation and dosing strategies in relation to preclinical and clinical efficacy/safety parameters, although it should be stressed that no head‐to‐head studies allow direct comparisons. This review also seeks to outline practical considerations involved with PTH prescribing and new directions in research regarding routes of administration. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Parathyroid Hormone and Parathyroid Hormone-Related Protein Analogs in Osteoporosis Therapy.

The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment. The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone. These analogs provide maximal benefit when their use is followed by a potent antiresorptive medication. Moreover, studies have shown that the combination of teriparatide and the RANK-ligand inhibitor, denosumab, increase bone density and estimated strength more than monotherapy and more than any currently available regimen. Parathyroid hormone and parathyroid hormone-related protein analogs, whether as monotherapy, in combination with antiresorptive agents or in sequence with antiresorptive agents, will likely play an expanding role in osteoporosis management.

Management of mineral and bone disorders in renal transplant recipients.

The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, pre-existing metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease. Patients should also be encouraged to take preventative measures against osteoporosis such as regular weight-bearing exercise, smoking cessation and reducing alcohol consumption. Biochemical abnormalities of disordered mineral metabolism should be corrected prior to transplantation wherever possible, and because these abnormalities commonly persist, post transplant hypophosphatemia, persistent hyperparathyroidism and low vitamin D levels should be regularly monitored and treated. Bone loss is greatest in the first 6-12months post-transplantation, during which period any intervention is likely to be of greatest benefit. There is strong evidence that bisphosphonates prevent post-transplantation bone loss; however, data are lacking that this clearly extends to a reduction in fracture incidence. Denosumab is a potential alternative to vitamin D receptor agonists and bisphosphonates in reducing post-transplantation bone loss; however, further studies are needed to demonstrate its safety in patients with a significantly reduced estimated glomerular filtration rate. Clinical judgement remains the cornerstone of this complex clinical problem, providing a strong rationale for the formation of combined endocrinology and nephrology clinics to treat patients with Chronic Kidney Disease-Mineral and Bone Disorder, before and after transplantation.

Effects of Long-Term Alendronate Treatment on a Large Sample of Pediatric Patients with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI. In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured. After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (P<.01). BMD at the lumbar spine and femoral neck significantly increased by 74.6% and 39.5%, with their BMD Z-score increasing from -3.0 to 0.1 and from -4.2 to -1.3, respectively (both P<.01 vs. baseline). In addition, serum ALP and β-CTX levels decreased by 35.6% and 44.3%, respectively (both P<.05 vs. baseline). Height significantly increased, but without an obvious increase in its Z-score. Patient tolerance of alendronate was good. Three years' treatment with alendronate was demonstrated for the first time to significantly reduce fracture incidence, increase lumbar spine and femoral neck BMD, and decrease bone turnover biomarkers in Chinese children and adolescents with OI. ALP = alkaline phosphatase β-CTX = cross-linked C-telopeptide of type I collagen BMD = bone mineral density BP = bisphosphonate DXA = dual-energy X-ray absorptiometry 25OHD = 25-hydroxyvitamin D OI = osteogenesis imperfecta PTH = parathyroid hormone.

Pamidronate treatment for osteogenesis imperfecta in black South Africans.

Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care.Objective. To assess the subjective attitude of patients towards pamidronate treatment. Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.