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  • Johansson, Sara, et al. (författare)
  • Subclinical hypervitaminosis A causes fragile bones in rats
  • 2002
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 31:6, s. 685-689
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Excessive intake of vitamin A has been associated with an increased risk of hip fracture in humans. This finding has raised the question of whether long-term intake of relatively moderate doses ("subclinical" hypervitaminosis A) contributes to fracture risk. Although it has been known for more than half a century that toxic doses of vitamin A lead to spontaneous fractures in rats, the lowest intake that induces adverse effects is not known, and the result of exposure to excessive doses that do not cause general toxicity has been rarely investigated. In this study, mature female rats were fed a standard diet with 12 IU vitamin A/g pellet (control, C), or standard diet supplemented with either 120 IU ("10 x C") or 600 IU ("50 x C") vitamin A/g pellet for 12 weeks. Fifteen animals were included in each group. The supplemented diets correspond to a vitamin A intake of approximately 1800 IU/day and 9000 IU/day, respectively. The latter dose is about one third of that previously reported to cause skeletal lesions. At the end of the study, serum retinyl esters were elevated 4- (p &lt; 0.01) and 20-fold (p &lt; 0.001) and the total amount of liver retinoid had increased 3- (p &lt; 0.001) and 7-fold (p &lt; 0.001) in the 10 x C and 50 x C group, respectively. The animals showed no clinical signs of general toxicity, and there were no significant bone changes in the 10 x C group. However, in the 50 x C group, a characteristic thinning of the cortex (cortical area -6.5% [p &lt; 0.001]) and reduction of the diameter of the long bones were evident (bone cross-sectional area -7.2% [p &lt; 0.01] at the midshaft and -11.0% [p &lt; 0.01] at the metaphysis), as measured by peripheral quantitative computed tomography. In agreement with these data and a decreased polar strength strain index (-14.0%, p &lt; 0.01), the three-point bending breaking force of the femur was reduced by 10.3% (p &lt; 0.01) in the 50 x C group. These data indicate that the negative skeletal effects appear at a subchronic vitamin A intake of somewhere between 10 and 50 times the standard diet. This level is considerably lower than previously reported. Our results suggest that long-term ingestion of modest excesses of vitamin A may contribute to fracture risk.</p>
  • Lammi, Pirkko, et al. (författare)
  • Site-specific immunostaining for type X collagen in noncalcified articular cartilage of canine stifle knee joint.
  • 2002
  • Ingår i: Bone. - Elsevier. - 8756-3282 .- 1873-2763. ; 31:6, s. 690-696
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Type X collagen is a short-chain collagen that is strongly expressed in hypertrophic chondrocytes. In this study, we used an immunohistochemical technique exploiting a prolonged hyaluronidase unmasking of type X collagen epitopes to show that type X collagen is not restricted to calcified cartilage, but is also present in normal canine noncalcified articular cartilage. A 30 degrees valgus angulation procedure of the right tibia was performed in 15 dogs at the age of 3 months, whereas their nonoperated sister dogs served as controls. Samples were collected 7 and 18 months after the surgery and immunostained for type X collagen. The deposition of type X collagen increased during maturation from age 43 weeks to 91 weeks. In the patella, most of the noncalcified cartilage stained for type X collagen, whereas, in the patellar surface of the femur, it was present mainly in the femoral groove close to cartilage surface. In femoral condyles, the staining localized mostly in the superficial cartilage on the lateral and medial sides, but not in the central weight-bearing area. In tibial condyles, type X collagen was often observed close to the cartilage surface in medial parts of the condyles, although staining could also be seen in the deep zone of the cartilage. Staining for type X collagen appeared strongest at sites where the birefringence of polarized light was lowest, suggesting a colocalization of type X collagen with the collagen fibril arcades in the intermediate zone. No significant difference in type X collagen immunostaining was observed in lesion-free articular cartilage between controls and dogs that underwent a 30 degrees valgus osteotomy. In osteoarthritic lesions, however, there was strong immunostaining for both type X collagen and collagenase-induced collagen cleavage products. The presence of type X collagen in the transitional zone of cartilage in the patella, femoropatellar groove, and in tibial cartilage uncovered by menisci suggests that it may involve a modification of collagen fibril arrangement at the site of collagen fibril arcades, perhaps providing additional support to the collagen network.</p>
  • Löfman, Owe, et al. (författare)
  • Bone mineral density in normal Swedish women
  • 1997
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 20:2, s. 167-174
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We examined 429 women, aged 20–80 years, randomly selected from the population register to establish normal values for bone mineral density (BMD) in Swedish women. BMD of the spine and hip was measured by dual-energy X-ray absorptiometry (DEXA; Hologic QDR 1000) and in the forearm by single photon absorptiometry (SPA; Molsgaard ND-1100). The recalled age of menarche was negatively correlated to BMD at all ages. There was no significant change in BMD from 20–49 years at any site except a slight decline at Ward's triangle. Bone loss was rapid at all sites during the first decade after menopause. Thereafter, BMD declined slowly in the trochanter and total hip but more rapidly in the forearm, femoral neck, and Ward's triangle. BMD in the spine even increased in the eighth decade probably due to osteoarthritis. The average change in forearm BMD during the 15 perimenopausal years comprising mean age for menopause ± 2 SD (43–57 years) was −0.4% per year in premenopausal females and −1.6% per year in postmenopausal females. The corresponding annual percental change was, for the spine, +0.2 and −1.7; neck, −0.7 and −1.7; trochanter, +0.5 and −1.5; and Ward's triangle, −0.1% and −2.2%, respectively. Our normal values for lumbar spine BMD prior to menopause did not differ from published values or the manufacturer's normal values; however, our spine BMD values for the first decade after menopause were significantly lower (≈10%) than in other studies. Our femoral neck BMD values for younger women were, like those of several other groups, significantly lower than the manufacturer's normal values, but our sample of young women in this study was small. The prevalence of osteoporosis, if defined as <em>t</em> score &lt; −2.5 is highly dependent on the sampling of the reference population of young adult women, and also on the choice of skeletal site. Further studies on bone mineral density in healthy young adult women are needed.</p>
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk
  • 2003
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 32:6, s. 694-703
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain, despite considerable research efforts. With the aim to examine these associations with an improved precision, we used data from a large population-based prospective cohort study in central Sweden. We estimated nutrient intake from a self-administered food-frequency questionnaire filled in by 60,689 women, aged 40-74 years at baseline during 1987-1990. During follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox proportional hazards models. We found no dose-response association between dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was 1.01 (95% CI 0.96-1.06) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 (95% CI 0.96-1.03). Furthermore, women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes: RR 1.07 (95% CI 0.92-1.24) and RR 1.00 (95% CI 0.79-1.27), respectively. Vitamin D intake was not associated with fracture risk. Furthermore, women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures (95% CI 0.88-1.17). Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women.</p>
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Use of low potency estrogens does not reduce the risk of hip fracture
  • 2002
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 30:4, s. 613-618
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50-81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67-1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58-1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61-1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49-0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.</p>
  • Abtahi, Jahan, et al. (författare)
  • A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
  • 2012
  • Ingår i: Bone. - Elsevier. - 8756-3282 .- 1873-2763. ; 50:5, s. 1148-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.</p>
  • Atroshi, Isam, et al. (författare)
  • Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men : a population-based case-control study
  • 2009
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 45:4, s. 789-793
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score&lt; or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.</p>
  • Binkley, Neil, et al. (författare)
  • Alendronate/vitamin D3 70 mg/2800 IU with and without additional 2800 IU vitamin D3 for osteoporosis : results from the 24-week extension of a 15-week randomized, controlled trial
  • 2009
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 44:4, s. 639-647
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Although vitamin D supplementation is a fundamental part of osteoporosis treatment, many patients do not regularly take adequate amounts. A once-weekly (OW) alendronate (ALN) preparation that includes 2800 IU of vitamin D3 in a single combination tablet (ALN+D2800) is available for treating patients and ensuring intake of vitamin D that is consistent with existing guidelines. This randomized, double-blind study extension was conducted to evaluate the safety and tolerability of ALN+D2800 and ALN+D2800 plus an additional 2800 IU vitamin D3 single tablet supplement (ALN+D5600) administered for 24 weeks in men and postmenopausal women with osteoporosis previously treated OW for 15 weeks with either ALN or ALN+D2800. The primary endpoint was the proportion of participants who developed hypercalciuria (defined as a 24-hour urine calcium &gt;300 mg in women or &gt;350 mg in men and an increase of &gt;25% versus randomization baseline) at week 39. The key secondary endpoint was the proportion of participants with vitamin D insufficiency (serum 25(OH)D &lt;15 ng/mL [37.4 nmol/L]) at the end of the study. Hypercalciuria incidence (4.2% [ALN+D5600] vs. 2.8% [ALN+D2800]), did not differ between groups (p = 0.354). No participants developed hypercalcemia. Among the participants with vitamin D insufficiency at the week 0 baseline, the prevalence of insufficiency at the end of the study was reduced by 92% in the ALN+D5600 group and by 86% in the ALN+D2800 group. The incidences of clinical adverse experiences, including drug-related adverse experiences, were similar in both groups. In subjects previously treated with ALN+D2800 for 15 weeks, the addition of 2800 IU D3 for 24 weeks did not produce hypercalcemia nor increase the risk of hypercalciuria.</p>
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