Improve Bone Mineral Density Research Articles

Male Hypogonadism (According to the Materials of the European Association of Urology)

Male hypogonadism is a clinical syndrome which is the result of insufficient production of the sex hormone testosterone by the testicles and the number of spermatozoa. The article reveals modern views on the physiology and pathophysiology of testosteroneogenesis in the male organism, provides information on the etiology, pathogenesis, classification, diagnosis and modern treatment of hypogonadism in men. Literature on the results of global and European researches in recent years, as well as materials of the Guideline of the European Association of Urology for 2022, were used in the article. An individual therapeutic approach to each patient with hypogonadism was demonstrated. The importance of diagnosis of chronic and systemic comorbid diseases that cause the risk of hypogonadism, the need to determine the body mass index and the measurement of waist circumference, the size of the testicles, the penis and the presence of secondary sexual characteristic was established. The article includes necessary biochemical and instrumental studies for the diagnosis of hypogonadism. Specific contraindications for hormone replacement therapy are identified. Absolute contraindications for testosterone therapy are indicated: topically widespread or metastatic prostate cancer (PC), breast cancer of men; men who desire to have children; hematocrit level >54%; uncontrolled or poorly controlled stagnant heart failure. Relative contraindications include IPSS>19, initial hematocrit of 48-50 %, venous thromboembolism in a family history. The article also provides recommendations for testosterone therapy. It has been proven that testosterone therapy improves mild forms of erectile dysfunction (ED) and libido in men with hypogonade states; improves the frequency of sexual intercourses, orgasm and general pleasure; increases low-fat mass, reduces fat and improves insulin resistance; normalizes body weight, waist circumference and lipid profile; relieves the symptoms of depression in men with hypogonadism; improves bone mineral density. It has been demonstrated that the use of testosterone therapy in eugonadal men is not indicated. Testosterone therapy should be used as first-line treatment in patients with symptomatic hypogonadism and moderate ED. In addition, it is necessary to use a combination of type 5 phosphodiesterase inhibitors and testosterone treatment in more severe ED forms. It is also necessary to use standard medical treatments for severe symptoms of depression and osteoporosis. The therapy of hypogonadism, non-medication and medication, the necessary medicines and the peculiarities of their use are widely described. The article shows that weight loss due to low calorie diet and regular physical activity leads to a slight improvement in testosterone levels, testosterone gels and prolonged injection drugs are testosterone drugs have the best safety profile, and gonadotropin treatment can be used in men with secondary hypogonadism. It is noted that before the treatment with testosterone, it is necessary to treat organic causes of hypogonadism (for example, pituitary tumors, hyperprolactinemia, etc.), improve lifestyle and reduce body weight in persons with obesity; cancel drugs that can impair testosterone production. Much attention is paid to the risk factors by the treatment with testosterone. Testosterone therapy is contraindicated for men with secondary hypogonadism who wish fertility, men with active PC or breast cancer. Restoration of testosterone concentration in serum relieves the symptoms and signs of hypogonadism in men after 3 months of treatment. Therefore, testosterone therapy leads to improvement of the quality of patient’s life.

Lessons learned from long-term side effects after zoledronic acid infusion following denosumab treatment: a case report and review of the literature

BackgroundZoledronic acid is an intravenous, highly potent aminobisphosphonate for use in patients with primary or secondary osteoporosis. Zoledronic acid-induced prolonged side-effects are well known and quite common. However, severe side-effects can be a threat to life. We report a case of severe side-effects induced by zoledronic acid infusion, and its positive effect on long-term back pain.Case presentationIn 2012, a 62-year-old white native Finnish woman was operated on for an estrogen and progesterone receptor-positive breast cancer. After radiotherapy, an aromatase inhibitor (letrozole) was started. Nine months after the operation, the patient suffered a low-energy compression fracture of Th XII. She received denosumab to prevent fragility fractures and to improve bone mineral density. Letrozole was discontinued after 5.5 years, and the last denosumab injection was given after 7 years. Six months later, at the age of 71 years, the patient received a single intravenous zoledronic acid infusion. Suddenly, at 10 hours from the infusion, she complained of severe trismus, muscle twitching, spasms, and tingling, matching hypocalcemia and several other symptoms. Her serum 25-hydroxyvitamin D concentration was high (163 nmol/L), the concentration of serum calcium and calcium-ion was normal (2.32 mmol/L and 1.23 mmol/L, respectively). However, the neutrophil to lymphocyte ratio (NLR) was low (1.6). A complete recovery took 2 months. Zoledronic acid infusion also had a positive effect: for many years, the patient had suffered low back pain and strain, which came to an end after this single infusion.ConclusionIt is important that the potential patients receive sufficient information about the possibility of side-effects following the administration of intravenous zoledronic acid. To ensure that a zoledronic acid infusion is given as safely as possible, the safety information should include that the patient should not be left without monitoring for a minimum 24 hours after the infusion. Being alone and experiencing serious side-effects may lead to acute cardiac problems. Furthermore, the chronic low back pain and strain that our patient suffered for many years has clearly reduced for 16 months after infusion, so far. We conclude that this is a positive effect of zoledronic acid.

Retrospective analyses of clinical features in 28 Chinese patients with type V osteogenesis imperfecta: new perspectives in an old issue

SummaryType V osteogenesis imperfecta (OI) is a form of OI characterized by radial head dislocation (RHD), calcification of interosseous membrane (CIM), and hyperplastic callus (HPC). In this study, we characterized the clinical features of 28 type V OI patients. We presented that dysfunctions of elbow, hip joint, and abnormal epiphyseal growth plate were associated with ectopic calcification and summarized the history of HPC progression and treatment.IntroductionThe current study aims to systematically characterize the skeletal phenotypes of patients with type V OI and suggested possible surgical solutions.MethodsA total of 28 patients were admitted for inpatient care at The Hong Kong University-Shenzhen Hospital diagnosed with type V OI (either clinically diagnosed or genetically confirmed with the IFITM5 c.-14C > T mutation).ResultsPrevalence of type V radiological features was comparable to previous literatures (RHD, 100%; CIM, 100%; HPC, 44%; and scoliosis, 50%). Novel skeletal phenotypes were presented including extension of coronoid process, acetabular labrum, acetabular protrusion, spontaneous autofusion of the hip, bulbous epiphysis, and popcorn calcification. Significant increase in BMD was observed in patients with bisphosphonate treatment. Twenty-five percent (3/12) of patients with preoperative use of indomethacin developed HPC postoperatively, and HPCs were absorbed in 2 young patients 2 years later.ConclusionThis retrospective study summarized the clinical features and highlighted the abnormalities in elbow, hip joint, and growth plate in type V OI patients. Our study contributed to a more comprehensive clinical spectrum of type V OI. We also characterized the natural progression of HPC formation and resorption in patients in different ages. The use of bisphosphonate treatment is effective in improving bone mineral density in type V OI patients, and whether indomethacin can reduce incidence of HPC formation deserves further investigation.

Application of carbon-coated nanomultilayer sintered porous titanium microprosthesis for the repair of osteochondral defects of the knee joint

We constructed a carbon-coated nanomultilayer (CNM) sintered porous titanium (Ti) microprosthesis for the optimal treatment of osteochondral defects of the knee joint. Physicochemical property tests revealed that the porosity of the constructed porous Ti-CNM prosthesis was ∼75%, while the pore size ranged 300–400 μm. The prosthesis had an elastic modulus (9.18 GPa) and compressive strength (98.3 MPa) similar to bone tissue. Furthermore, the CNM effectively reduced the roughness of the prosthesis surface. In animal experiments, the porous Ti-CNM improved the mineralization ability of osteoblasts in bone defects, as indicated by antialkaline phosphatase and osteocalcin, and improved bone mineral density, trabecular thickness, average trabecular number, and cortical bone thickness in the defective regions, thereby shortening the repair time. In addition, porous Ti-CNM effectively improved the production of extracellular matrix components in cartilage defects, such as collagen I, collagen II, and aggrecan, thereby enhancing the repair of cartilage defects and effectively preventing the degeneration of the opposite joint. The porous Ti-CNM prosthesis thus demonstrates great therapeutic potential for middle-aged patients with osteoarthritis.

Medical optimization of osteoporosis for adult spinal deformity surgery: a state-of-the-art evidence-based review of current pharmacotherapy.

Osteoporosis is a common, but challenging phenomenon to overcome in adult spinal deformity (ASD) surgery. Several pharmacological agents are at the surgeon's disposal to optimize the osteoporotic patient prior to undergoing extensive reconstruction. Familiarity with these medications will allow the surgeon to make informed decisions on selecting the most appropriate adjuncts for each individual patient. A comprehensive literature review was conducted in PubMed from September 2021 to April 2022. Studies were selected that contained combinations of various terms including osteoporosis, specific medications, spine surgery, fusion, cage subsidence, screw loosening, pull-out, junctional kyphosis/failure. Bisphosphonates, denosumab, selective estrogen receptor modulators, teriparatide, abaloparatide and romosozumab are all pharmacological agents currently available for adjunctive use. While these medications have been shown to have beneficial effects on improving bone mineral density in the osteoporotic patient, varying evidence is available on their specific effects in the context of extensive spine surgery. There is still a lack of human studies with use of the newer agents. Bisphosphonates are first-line agents due to their low cost and robust evidence behind their utility. However, in the absence of contraindications, optimizing bone quality with anabolic medications should be strongly considered in preparation for spinal deformity surgeries due to their beneficial and favorable effects on fusion and hardware compared to the anti-resorptive medications.

Comparison of denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis

BackgroundBoth denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove the clinical results between denosumab and bisphosphonates. This meta-analysis aims to compare the efficacy and safety between denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis through evidence-based medicine.MethodsMEDLINE, EMBASE, and the Cochrane library databases were searched up to June 2022 for randomized controlled trials that compared denosumab and oral bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. The following outcomes were extracted for comparison: percentage change in bone mineral density from baseline at the lumbar spine, total hip, femoral neck, and ultra-distal radius; percentage change from baseline in serum concentration of bone turnover markers; and incidence of treatment-emergent adverse events.ResultsFour randomized controlled trials involving 714 patients were included. The pooled results showed that denosumab was superior to bisphosphonates in improving bone mineral density in lumbar spine (mean difference (MD) 1.70; 95% confidence interval (CI) 1.11–2.30; P < 0.001) and ultra-distal radius (MD 0.87; 95% CI 0.29–1.45; P = 0.003), and in suppressing C-terminal telopeptide of type 1 collagen (MD -34.83; 95% CI -67.37--2.28; P = 0.04) and procollagen type 1 N-terminal propeptide (MD -14.29; 95% CI -23.65- -4.94; P = 0.003) at 12 months. No significant differences were found in percentage change in total hip or femoral neck bone mineral density at 12 months, or in the incidence of treatment-emergent adverse events or osteoporosis-related fracture.ConclusionsCompared with bisphosphonates, denosumab is superior in improving bone mineral density in lumbar spine and ultra-distal radius for glucocorticoid-induced osteoporosis. Further studies are needed to prove the efficacy of denosumab.

Do Serum 25-Hydroxyvitamin D Concentrations Affect Body Composition, Physical Fitness, Bone Strength and Bone Biomarkers in Female Children and Adolescent Football Players? A One-Season Study.

The aim was to compare changes in body composition, physical fitness, and bone biomarkers in female children and adolescent football players with different Vitamin D levels. Twenty-two players were classified into two groups according to 25(OH)D concentrations: 11 with deficient/insufficient 25(OH)D levels (IVD; <30 ng/mL) and 11 with sufficient 25(OH)D levels (SVD; ≥30 ng/mL). Body composition parameters were measured using dual-energy X-ray absorptiometry and a peripheral quantitative computed tomography scanner. The following physical fitness tests were applied: maximal isometric knee extension (MIF), long jump, 30-m sprint, and 20-m shuttle run test (VO2max). Electrochemiluminescence immunoassays were used to analyze bone biomarkers and 25(OH)D. All variables were registered at the beginning and the end of the football season. The increase in subtotal bone mineral density (BMD) was higher in players with SVD than those with IVD (p = 0.030). Only players with SVD improved their MIF of the left leg (p = 0.005); whereas, only players with IVD decreased their 30-m sprint performance (p = 0.007) and VO2max (p = 0.046). No significant between- and within-group differences were found for bone biomarkers. SVD might cause an extra improvement of subtotal BMD in female children and adolescent football players. Moreover, it seems that the 25(OH)D concentration could be an important parameter for physical fitness improvement in this population.

Celiac disease and bone.

Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65years) were combined. Dietary intake was assessed with food records (2, 3 or 7days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

BackgroundSenile osteoporosis (SOP) is one of the most prevalent diseases that afflict the elderly population, which characterized by decreased osteogenic ability. Glucosamine (GlcN) is an over-the-counter dietary supplement. Our previous study reported that GlcN promotes osteoblast proliferation by activating autophagy in vitro. The purpose of this study is to determine the effects and mechanisms of GlcN on senile osteoporosis and osteogenic differentiation in vivo.MethodsAging was induced by subcutaneous injection of d-Galactose (d-Gal), and treated with GlcN or vehicle. The anti-senile-osteoporosis effect of GlcN was explored by examining changes in micro-CT, serum indicators, body weight, protein and gene expression of aging and apoptosis. Additionally, the effects of GlcN on protein and gene expression of osteogenesis and autophagy were observed by inhibiting autophagy with 3-methyladenine (3-MA).ResultsGlcN significantly improved bone mineral density (BMD) and bone micro-architecture, decreased skeletal senescence and apoptosis and increased osteogenesis in d-Gal induced osteoporotic mice. While all effect was reversed with 3-MA.ConclusionGlcN effectively delayed the progression of osteoporosis in senile osteoporotic mice by promoting osteoblast autophagy. This study suggested that GlcN may be a prospective candidate drug for the treatment of SOP.

Compound of Cynanchum wilfordii and Humulus lupulus L. Ameliorates Menopausal Symptoms in Ovariectomized Mice.

Cynanchum wilfordii and Humulus lupulus L. have been used for their various pharmacological properties in South Korea as a traditional medicine or health functional food, respectively, and their intake may relieve menopausal symptoms. The purpose of current study was to determine the effect of compound of Cynanchum wilfordii and Humulus lupulus L. (CWHL) in menopausal symptoms of ovariectomized (OVX) mice. OVX mice received CWHL or caudatin (an active ingredient of CWHL) once daily for 7weeks. Values for hypothalamic serotonin (5-HT), dopamine, norepinephrine, estrogen receptor (ER)-β, 5-HT1A, and 5-HT2A were significantly enhanced, while value for hypothalamic monoamine oxidase A was reduced in CWHL and caudatin groups compared with the OVX group. CWHL and caudatin significantly reduced tail skin temperature and rectal temperature of OVX mice through partial recovering of the levels of serum estrogen, nitric oxide, follicle-stimulating hormone, luteinizing hormone, and receptor-activator of the NF-κB ligand (RANKL). Moreover, CWHL and caudatin improved bone mineral density via decreasing levels of serum RANKL, tartrate-resistant acid phosphatase, and collagen type 1 cross-linked N-telopeptide and improving levels of serum alkaline phosphatase, osteoprotegerin, and osteocalcin compared with the OVX group without adverse effects such as dyslipidemia. CWHL increased uterine ER-β levels but did not change uterus and vaginal weights. Taken together, the results indicate that CWHL may relieve menopausal symptoms by controlling depression-, hot flashes-, and osteoporosis-associated biomarkers. Therefore, we propose that CWHL might be a safe and potential candidate for management of menopause as a health functional food.

Impact of an exercise program in children with inflammatory bowel disease in remission.

The aim of our study was to investigate the impact of a structured exercise program on bone mineral density (BMD) and body composition parameters in children and adolescents with IBD in remission. Patients were recruited to participate in a 6-month exercise program. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD. The same method was used to assess fat mass (FM) and lean body mass (LBM) at baseline and at the completion of the program. Based on the baseline and endpoint TBLH DXA measurements, a total of 42 study participants (25 boys; aged 15.3 ± 2.08 years) experienced an increase in BMD (from 0.959 ± 0.023 g/cm2 to 0.988 ± 0.025 g/cm2, p < 0.001) and LBM (from 37.12 ± 1.43 kg to 38.75 ± 1.61 kg, p = 0.012). Age- and sex-based BMD Z-score increased significantly (from -0.35 ± 0.15 to -0.28 ± 0.17, p = 0.020), whilst LBM Z-score did not significantly change (from -1.78 ± 0.23 to -1.71 ± 1.49, p = 0.908). There was a significant improvement in BMD, age- and sex-based BMD Z-score, and LBM amongst study participants. Subgroup analysis showed that patients with CD and male study participants experienced significant improvement in all parameters, whilst patients with UC and IBD-U and female patients experienced improvement solely in BMD. Children and adolescents with IBD, regardless of disease activity, are under increased risk of secondary osteoporosis and lean body mass deficits. A 6-month home-based structured exercise program leads to a significant improvement in bone mineral density and lean body mass. Exercise therapy should be explored as a potentially adjacent to standard treatment modalities.

OR25-6 In Men on Testosterone Therapy, Baseline Testosterone Level of &amp;lt;264 ng/dL is Associated with Greater Improvement in Body Composition, While Level of ≥264 ng/dL Favors Improvement in Metabolic Profile

Abstract Context Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of &amp;lt;200 ng/dL is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study investigating whether baseline T levels also influences body composition and metabolic response to T therapy. Objective To determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with baseline T level of &amp;lt; 264 ng/dL compared to those with levels ≥264ng/dL Methods: Secondary analysis of single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 involving 105 men (40-74 years old), with average morning T &amp;lt; 300 ng/dL, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of &amp;lt; 264 ng/dL (N=43) and those with ≥264 ng/dL (N=57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, sclerostin), adiponectin, and leptin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD, and body composition by dual-energy x-ray absorptiometry (DXA). Results Men with T &amp;lt; 264 ng/dL showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dL (4.2±4.1 vs 2.7±3.8%; p=0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7±11.5 vs 4.4±4.3%, 7.3±11.6 vs 2.4±6.8%; p=0.033 and p=0.043, respectively). Men with T ≥ 264 ng/dL showed significant decreases in HbA1c at 12 months (-3.1±9.2 vs 3.2±13.9%; p=0.005), fasting glucose at 18 months (-4.2±31.9 vs 13.0±57.3%; p=0.040), LDL at 6 months (-6.4±27.5 vs 12.8±44.1%; p=0.034), leptin at 18 months (-40.2±35.1 vs -27.6±31.0%; p=0.034) compared to those with T &amp;lt; 264 ng/dL. No significant differences in BMD and bone turnover markers were observed. Conclusion T therapy results in improvement in body composition irrespective of baseline T levels but T &amp;lt;264 ng/dL is associated with greater improvement in FFM, whereas T level of ≥264 ng/dL favors improvement in metabolic profile. Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.

Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient With Hypophosphatasia

Hypophosphatasia is a rare, inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with hypophosphatasia are limited because of concerns for a greater likelihood of atypical femoral fractures with antiresorptive agents. We report here the case of a patient with hypophosphatasia and osteoporosis who was treated with romosozumab-aqqg (Romo). An 81-year-old woman presented for management of osteoporosis with multiple fractures. She experienced a decline in bone mineral density over 20 years despite sequential osteoporosis treatment with oral bisphosphonates, hormone replacement therapy, teriparatide, and denosumab. Hypophosphatasia was suspected because of low serum alkaline phosphatase levels and was confirmed by genetic testing. After diagnosing hypophosphatasia, bone mineral density continued to decline and a trial of Romo was begun. After 1 year of Romo therapy, bone mineral density improved by 21%, and 10% at the lumbar spine and total hip, respectively. These changes were substantially greater than what she had experienced with prior teriparatide therapy. Blood alkaline phosphatase remained low on Romo. To our knowledge, this is the first report of a patient with hypophosphatasia and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum alkaline phosphatase, but improved bone mineral density significantly. In conclusion, Romo is a potential treatment option for osteoporosis in patients with hypophosphatasia for whom limited alternatives exist.

What's New in Musculoskeletal Basic Science.

What's New in Musculoskeletal Basic Science.

Resistance training for postmenopausal women: systematic review and meta-analysis.

Numerous studies have been published assessing the effects of resistance muscle training to mitigate menopausal symptoms, given the endocrine muscle function and its metabolic regulation. Therefore, mapping and synthesizing high-quality studies are necessary to help clinical decisions. The aim of this study was to assess the effects (benefits and harms) of resistance muscle training for postmenopausal women. Electronic searches were conducted in MEDLINE (via PubMed), EMBASE, CENTRAL, PEDro, LILACS, and SPORTDiscus up to December 2021. Two independent reviewers selected the retrieved references and extracted relevant data from included studies. The methodological quality (risk of bias) using the Cochrane Risk of Bias table and the certainty of the evidence (GRADE approach) were assessed. Twelve randomized clinical trials (n = 452) with unclear to high risk of bias were identified. Compared with no exercise, resistance training (up to 16 weeks) seems to promote an improvement in functional capacity (mean difference [MD], 2.90 points; 95% CI, 0.60-5.20) and bone mineral density (MD, 0.10; 95% CI, 0.10-0.10) and a reduction in the hot flash frequency (13/29 vs 1/29; risk ratio, 13.0; 95% CI, 1.82-93.01) and fat mass (MD, -3.15; 95% CI, -6.68 to 0.38), and no differences were observed between groups regarding abdominal circumference and body mass index. When compared with aerobic exercises, resistance training may result in a reduction of hot flash frequency (7/18 vs 14/18; risk ratio, 0.50; 95% CI, 0.27-0.94) and fat mass (MD, -7.80; 95% CI, -14.02 to -1.58) and no difference in the quality of life and body mass index. Regarding safety, no serious adverse events were reported. Based on the GRADE approach, the certainty of this evidence was graded as very low to low, leading to imprecisely estimated effects. Resistance muscle training seems to improve postmenopausal symptoms and functional capacity. Given the low to very low certainty of the evidence, further randomized clinical trials with higher methodological quality and better reports are still needed. As an implication for clinical practice, health professionals should consider individualized aspects such as the previous history of exercise practice, physical capacity, and adaptation period.

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

Efficacy of Moxibustion for Primary Osteoporosis: A Trial Sequential Meta-Analysis of Randomized Controlled Trials.

Background Primary osteoporosis (PO) is a systemic metabolic skeletal disease. Previous studies have shown that moxibustion can reduce pain intensity and enhance response rate, bone mineral density (BMD), and living function of the patients with PO. However, consensus on its efficacy does not exist, and evidence of moxibustion for PO is also insufficient. Methods We searched five English and four Chinese databases with various additional sources and published reviews through December 1, 2021, to evaluate potentially concerned randomized controlled trials (RCTs). Two independent researchers addressed selection screening, data extraction, and risk of bias assessment. The data of this meta-analysis were analyzed using the RevMan v.5.4 software. Additionally, the trial sequential analysis v.0.9.5.10 β was used to estimate the sample size. In contrast, the quality of evidence from the RCTs was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results The current meta-analysis included 14 RCTs containing 898 participants. The methodological quality of the RCTs was moderate. The review demonstrated that a combination of moxibustion and conventional medicine (CM) significantly reduced pain intensity and improved the BMD compared with CM. Furthermore, it was found that moxibustion plus CM/moxibustion could improve response rates compared with CM. However, it was found that the reduction of pain intensity and improvement of BMD by moxibustion showed no significant difference compared with CM. It was also evident that the sample size of most outcomes was inadequate. Moreover, all evidence obtained in this study was ranked as low to critically low. Conclusions In conclusion, it was demonstrated that moxibustion is a potentially effective agent for treating PO. However, high-quality studies should be implemented in the future because this study only obtained low-quality evidence. This study was registered in the PROSPERO platform (CRD42021291310).

A multi-model approach to predict efficacious clinical dose for an anti-TGF-β antibody (GC2008) in the treatment of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited bone dysplasias characterized by reduced skeletal mass and bone fragility. Although the primary manifestation of the disease involves the skeleton, OI is a generalized connective tissue disorder that requires a multidisciplinary treatment approach. Recent studies indicate that application of a transforming growth factor beta (TGF-β) neutralizing antibody increased bone volume fraction (BVF) and strength in an OI mouse model and improved bone mineral density (BMD) in a small cohort of patients with OI. In this work, we have developed a multitiered quantitative pharmacology approach to predict human efficacious dose of a new anti-TGF-β antibody drug candidate (GC2008). This method aims to translate GC2008 pharmacokinetic/pharmacodynamic (PK/PD) relationship in patients, using a number of appropriate mathematical models and available preclinical and clinical data. Compartmental PK linked with an indirect PD effect model was used to characterize both pre-clinical and clinical PK/PD data and predict a GC2008 dose that would significantly increase BMD or BVF in patients with OI. Furthermore, a physiologically-based pharmacokinetic model incorporating GC2008 and the body's physiological properties was developed and used to predict a GC2008 dose that would decrease the TGF-β level in bone to that of healthy individuals. By using multiple models, we aim to reveal information for different aspects of OI disease that will ultimately lead to a more informed dose projection of GC2008 in humans. The different modeling efforts predicted a similar range of pharmacologically relevant doses in patients with OI providing an informed approach for an early clinical dose setting.

Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials.

ObjectiveTo evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis.MethodsThe literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis.ResultsA total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events.ConclusionProbiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.