Tag Archives: human

Tylenol is a Risk Factor for Fracture in Women

Abstract

Paracetamol (acetaminophen) use, fracture and bone mineral density.

Paracetamol is the most widely prescribed simple analgesic and antipyretic. It exerts its effects via cyclooxygenase and endocannabinoid pathways, which may affect signalling in bone cells and hence influence bone metabolism. Given the high rates of paracetamol use in the community and the evidence linking its mechanism of action to bone metabolism, we aimed to investigate the association between paracetamol use, fracture, and bone mineral density (BMD) in women participating in the Geelong Osteoporosis Study (GOS). Cases (n = 569) were women aged ≥ 50 years identified from radiological reports as having sustained a fracture between 1994 and 1996. Controls (n = 775) were women without fracture recruited from the same region during this period. BMD was measured at the spine, hip, total body and forearm using dual energy absorptiometry. Medication use, medical history and lifestyle factors were self-reported. There were 69 (12.1%) paracetamol users among the cases and 63 (8.1%) among the controls. Paracetamol use increased the odds for fracture (OR = 1.56, 95%CI 1.09-2.24, p = 0.02). Adjustment for BMD at the spine, total hip and forearm did not confound the association. However, incorporating total body BMD into the model attenuated the association (adjusted OR = 1.46, 95%CI 1.00-2.14, p = 0.051). Further adjustment for age, weight, physical activity, smoking, alcohol, calcium intake, medication use, medical conditions, falls and previous fracture did not explain the association. These data suggest that paracetamol use is a risk factor for fracture, although the mechanism of action remains unclear.

Williams LJ, Pasco JA, Henry MJ, Sanders KM…
Bone Jun 2011
PMID: 21396491

Vitamin D3 + K2 + Sr + Mg + DHA as Effective as Bisphosphonates in Women

Abstract

Combination of Micronutrients for Bone (COMB) Study: bone density after micronutrient intervention.

Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micronutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micronutrient therapy with a combination that included vitamin D(3), vitamin K(2), strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals where bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.

Genuis SJ, Bouchard TP
J Environ Public Health 2012
PMID: 22291722 | Free Full Text

Prickly Pear Improves Bone Density in Women

Abstract

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis.
To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM).
The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD.
After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal).
The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Aguilera-Barreiro Mde L, Rivera-Márquez JA, Trujillo-Arriaga HM, Tamayo Y Orozco JA…
Food Nutr Res 2013
PMID: 23704856 | Free Full Text

Beta Blocker Prevents Bone Loss in Pediatric Burn Patients

Abstract

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.
Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear.
One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant.
Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used.
Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Herndon DN, Rodriguez NA, Diaz EC, Hegde S…
Ann. Surg. Sep 2012
PMID: 22895351

Beta Blocker Lowers Fracture Risk in Men and Women

Abstract

Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study.

In animal model, mice treated with beta-blockers (BB) had increased bone mass. In humans, high bone mass is associated with reduce fracture risk. The present study sought to test the hypothesis that BB use is associated with reduced fracture risk.
Data from 3488 participants (1285 men) aged 50 years and above in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Baseline characteristics of participants were obtained at the initial visit which had taken place between 1989 and 1993. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). Two hundred and sixty two (20%) men and 411 (19%) women had been on BB, as ascertained by direct interview and verification with medication history. The incidence of fragility fractures was ascertained during the follow-up period (1989-2008).
In men, BB use was associated with higher BMD at the femoral neck (0.96 versus 0.92 g/cm², P < 0.01), higher lumbar spine (1.32 versus 1.25 g/cm², P < 0.01), and lower fracture risk than those not on BB (odds ratio [OR]: 0.49; 95% CI: 0.32-0.75). In women, BB users also had higher femoral neck BMD (0.83 versus 0.81 g/cm², P < 0.01), higher lumbar spine BMD (1.11 versus 1.06 g/cm², P < 0.01), and lower risk of fracture than non-users (OR 0.68, 95% CI: 0.53-0.87). The associations between BB use and fracture risk were independent of age, BMD, and clinical risk factors. Subgroup analysis suggested that the association was mainly found in selective BB, not in non-selective BB.
Beta-blockers use, particularly selective BB, was associated with reduced fracture risk in both men and women, and the association was independent of BMD.

Yang S, Nguyen ND, Center JR, Eisman JA…
Bone Mar 2011
PMID: 21047567

Review: Beta Blockers in Space

Abstract

Sympathetic neural influence on bone metabolism in microgravity (Review).

Bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space and also for bedridden elderly people. Recent studies have indicated that the sympathetic nervous system plays a role in bone metabolism. This paper reviews findings concerning with sympathetic influences on bone metabolism to hypothesize the mechanism how sympathetic neural functions are related to bone loss in microgravity. Animal studies have suggested that leptin stimulates hypothalamus increasing sympathetic outflow to bone and enhances bone resorption through noradrenaline and β-adrenoreceptors in bone. In humans, even though there have been some controversial findings, use of β-adrenoblockers has been reported to be beneficial for prevention of osteoporosis and bone fracture. On the other hand, microneurographically-recorded sympathetic nerve activity was enhanced by exposure to microgravity in space as well as dry immersion or long-term bed rest to simulate microgravity. The same sympathetic activity became higher in elderly people whose bone mass becomes generally reduced. Our recent findings indicated a significant correlation between muscle sympathetic nerve activity and urinary deoxypyridinoline as a specific marker measuring bone resorption. Based on these findings we would like to propose a following hypothesis concerning the sympathetic involvement in the mechanism of bone loss in microgravity: An exposure to prolonged microgravity may enhance sympathetic neural traffic not only to muscle but also to bone. This sympathetic enhancement increases plasma noradrenaline level and inhibits osteogenesis and facilitates bone resorption through β-adrenoreceptors in bone to facilitate bone resorption to reduce bone mass. The use of β-adrenoblockers to prevent bone loss in microgravity may be reasonable.

Mano T, Nishimura N, Iwase S
Acta Physiol Hung Dec 2010
PMID: 21138811

Beta Blockers Associated with Fractures in Postmenopausal Women with Heart Disease

Abstract

Beta-blocker use is associated with fragility fractures in postmenopausal women with coronary heart disease.

An association between cardiovascular disease and osteoporosis is described. A number of drugs often used by patients with coronary heart disease, such as thiazides, statins and beta-blockers, have shown controversial effects on bone. 1) To study the possible association between coronary heart disease (CHD) and bone mass density (BMD), quantitative ultrasound measurements (QUS) and the prevalence of fragility and vertebral fractures. 2) To study the possible influence of a number of drugs, statins, thiazides and beta-blockers, on BMD and fractures.
Case-control study performed on 74 postmenopausal women who had recently suffered from CHD, and 111 age-matched controls. BMD was measured by Dual X-Ray Absorptiometry (DXA) at the lumbar spine and proximal femur. Quantitative Ultrasound (QUS) was also measured at the heel. Vertebral fractures were diagnosed by lateral, thoracic and lumbar X-rays. The occurrence of non-vertebral fractures was determined by examination of medical records.
Patients with CHD had higher values of BMI. They had a higher prevalence of arterial hypertension and hyperlipidemia, and consequently higher consumption of beta-blockers and statins, but not of thiazides, and had lower alcohol consumption. Patients with CHD had higher BMD values, measured by DXA at the proximal femur, than controls, but there were no differences in DXA values at the lumbar spine or QUS at the heel between the two groups. The prevalence of all fragility factures was slightly higher in patients with CHD, but not to a significant extent. The prevalence of vertebral fractures was similar in the two groups. In a logistic analysis to identify factors associated with all fractures, beta-blockers were positively associated with fragility fractures, and DXA at the femoral neck was inversely associated with fragility fractures.
Postmenopausal women with CHD have higher values of BMD at the proximal femur but, despite this, show a slight but non-significant increase in the prevalence of fragility fractures. Beta-blockers are independently associated with fragility fractures, but thiazides and statins are not.

Sosa M, Saavedra P, Gómez de Tejada MJ, Mosquera J…
Aging Clin Exp Res Apr 2011
PMID: 20463439

Beta Blockers May Blunt Exercise Benefits

Abstract

β-Adrenergic receptor blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in humans.

β-Adrenergic receptor (AR) signaling is a regulator of skeletal muscle protein synthesis and mitochondrial biogenesis in mice. We hypothesized that β-AR blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in adult humans. Six healthy men (mean ± SD: 26 ± 6 yr old, 39.9 ± 4.9 ml·kg(-1)·min(-1) peak O(2) uptake, 26.7 ± 2.0 kg/m(2) body mass index) performed 1 h of stationary cycle ergometer exercise (60% peak O(2) uptake) during 1) β-AR blockade (intravenous propranolol) and 2) administration of saline (control). Skeletal muscle mitochondrial, myofibrillar, and sarcoplasmic protein synthesis rates were assessed using [(2)H(5)]phenylalanine incorporation into skeletal muscle proteins after exercise. The mRNA content of signals for mitochondrial biogenesis was determined using real-time PCR. β-AR blockade decreased mitochondrial (from 0.217 ± 0.076 to 0.135 ± 0.031%/h, P < 0.05), but not myofibrillar or sarcoplasmic, protein synthesis rates. Peroxisome proliferator-activated receptor-γ coactivator-1α mRNA was increased ∼2.5-fold (P < 0.05) at 5 h compared with 1 h postexercise but was not influenced by β-AR blockade. We conclude that decreased β-AR signaling during cycling can blunt the postexercise increase in mitochondrial protein synthesis rates without affecting mRNA content.

Robinson MM, Bell C, Peelor FF, Miller BF
Am. J. Physiol. Regul. Integr. Comp. Physiol. Aug 2011
PMID: 21613574 | Free Full Text

Given that increased muscle tends to increase bone, this is somewhat negative, even though there is some evidence that beta blockers plus exercise is additive for bone.

Guduchi Increases Osteoblasts and Mineralization In Vitro

Abstract

Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro.

Ancient Indian ayurvedic literature prescribes Tinospora cordifolia as a remedy to rheumatoid arthritis, inflammatory and allied diseases of musculo skeletal system. To investigate the effects of the alcoholic extract of Tinospora cordifolia (TC) on the proliferation, differentiation and mineralization of bone like matrix on osteoblast model systems in vitro and hence its possible use as a potential anti-osteoporotic agent.
Two in vitro osteoblast model systems were used in the study viz., human osteoblast-like cells MG-63 and primary osteoblast cells isolated from femur of rats. Cell growth and viability was assessed by standard colorimetric assays like MTT assay. The cell differentiation into osteoblastic lineage was evaluated by the activities of bone marker alkaline phosphatase. The effect of the extract on matrix mineralization was assessed by alizarin red-s staining and Von kossa staining. Cell morphology was studied by phase contrast microscopy and light microscopy (Giemsa/crystal violet staining).
Results indicate that the alcoholic extract of TC at a dosage of 25μg/ml stimulated the growth of osteoblasts, increased the differentiation of cells into osteoblastic lineage and increased the mineralization of bone like matrix on both the osteoblast model systems used in the study. Cell morphology studies clearly indicated the increase in cell numbers and absence of adverse change in the cell morphology on treatment with the extract.
TC extract has a potential influence on osteogenesis and hence its use could be explored as a potential anti-osteoporotic agent.

Abiramasundari G, Sumalatha KR, Sreepriya M
J Ethnopharmacol May 2012
PMID: 22449439

Berberine + D3 + K1 + Hop Rho Iso-α-Acids Improves Bone Profile in Postmenopausal Women

Abstract

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome.

Lamb JJ, Holick MF, Lerman RH, Konda VR…
Nutr Res May 2011
PMID: 21636012