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Genetic factors play an important role in the development of osteoporosis. Several monogenic forms of osteoporosis have been recognized, most recently an X-chromosomal form resulting from mutations in the gene encoding plastin 3 (PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeleton. We present a large family with early onset osteoporosis and X-linked inheritance. Phenotyping was performed on 19 family members and whole-exome sequencing on 7 family members (5 with a diagnosis of early onset osteoporosis and 2 with normal bone parameters). Osteoporosis had its onset in childhood and was characterized by recurrent peripheral fractures, low bone mineral density (BMD), vertebral compression fractures, and significant height loss in adulthood. Males were in general more severely affected than females. Bone histomorphometry findings in 4 males and 1 female showed severe trabecular osteoporosis, low amount of osteoid, and decreased mineral apposition rate, indicating impaired bone formation; resorption parameters were increased in some. All affected subjects shared a single base substitution (c.73-24T > A) in intron 2 of PLS3 on Xq23. The mutation, confirmed by Sanger sequencing, segregated according to the skeletal phenotype. The mutation introduces a new acceptor splice site with a predicted splice score of 0.99 and, thereby, as confirmed by cDNA sequencing, induces the insertion of 22 bases between exons 2 and 3, causing a frameshift and premature termination of mRNA translation (p.Asp25Alafs à 17). The mutation affects the first N-terminal calcium-binding EF-hand domain and abolishes all calcium-and actin-binding domains of the protein. Our results confirm the role of PLS3 mutations in early onset osteoporosis. The mechanism whereby PLS3 affects bone health is unclear, but it may be linked to osteocyte dendrite function and skeletal mechanosensing. Future studies are needed to elucidate the role of PLS3 in osteoporosis and to define optimal treatment.

ObjectiveTo assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus.MethodsIn this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35–65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out.ResultsIn the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, −4.3; 95% CI, −11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (−3.2; −8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (−0.4; −1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups.ConclusionsIn this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.

Severe vitamin D deficiency causes rickets, but scarce data are available about the extent to which vitamin D status determines the development of the peak bone mass in young adults. Our aim was to evaluate the prevalence of vitamin D deficiency [serum 25-hydroxyvitamin D (25-OHD) less than the lower limit of the reference range of 20-105 nmol/liter] and the relationship between vitamin D status and peak bone mass among young Finnish men. A cross-sectional study of determinants of peak bone mass with data on lifestyle factors collected retrospectively was performed in 220 young men, aged 18.3-20.6 yr. One hundred and seventy men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, bone mineral density, and scan area were measured in lumbar spine and upper femur by dual energy x-ray absorptiometry. Serum 25-OHD concentrations were followed prospectively for 1 yr. In July 2000, only 0.9% of the men had vitamin D deficiency, but 6 months later, in the winter, the respective percentage was 38.9%. After adjusting for age, height, weight, exercise, smoking, calcium, and alcohol intake, there existed a positive correlation between serum 25-OHD and bone mineral content at lumbar spine (P = 0.057), femoral neck (P = 0.041), trochanter (P = 0.010), and total hip (P = 0.025). The correlation coefficients for the bone mineral densities at the four measurement sites were 0.035, 0.061, 0.056, and 0.068, respectively. No correlation was found to scan area. We conclude that vitamin D deficiency is very common in Finnish young men in the winter, and it may have detrimental effects on the acquisition of maximal peak bone mass. As in Finland vitamin D supplementation to infants is now stopped at the age of 3 yr, it can be asked whether at our latitude it should be continued from that age onward, not for the prevention of rickets, but as prophylaxis for osteoporosis.

Bone grafting procedures are undergoing a major shift from autologous and allogeneic bone grafts to synthetic bone graft substitutes. Bioactive glasses are a group of synthetic silica-based bioactive materials with bone bonding properties first discovered by Larry Hench. They have several unique properties compared with other synthetic bioresorbable bioactive ceramics, such as calcium phosphates, hydroxyapatite (HA) and tricalcium phosphate (TCP). Bioactive glasses have different rates of bioactivity and resorption rates depending on their chemical compositions. The critical feature for the rate of bioactivity is a SiO 2 content <60% in weight. In vivo, the material is highly osteoconductive and it seems to promote the growth of new bone on its surface. In a recent study, the activity of the material was found even to overshadow the effect of BMP-2 gene therapy. In vivo, there is a dynamic balance between intramedullary bone formation and bioactive glass resorption. Recent studies of molecular biology have shown that bioactive glass induces a high local turnover of bone formation and resorption. Many osteoporotic fracture patients are candidates for concurrent treatment with bisphosphonates and bioceramic bone graft substitutes. Since osteopromotive silicabased bioactive glasses induce accelerated local bone turnover, adjunct antiresorptive agents may affect the process. However, a recent study showed that an adjunct antiresorptive therapy (zoledronic acid) is even beneficial for bone incorporation of bioactive glass. Based on these observations, bioactive glasses are a promising group of unique biomaterials to act as bone graft substitutes.

To study the role of serum testosterone (T), estradiol (E(2)), and SHBG as regulators of peak bone mass and bone turnover rate in males, a cross-sectional study with data on lifestyle factors collected retrospectively was performed in 204 young Finnish men, 18.3-20.6 yr old. One hundred fifty-four men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, density, and scan area were measured in lumbar spine and upper femur by dual-energy x-ray absorptiometry. Blood was sampled for determination of serum total and free T, total and free E(2), SHBG, type I procollagen aminoterminal propeptide (PINP), total osteocalcin (TOC) and carboxylated osteocalcin (COC), and tartrate-resistant acid phosphatase 5b (TRACP5b); and urine was collected for determination of type I collagen aminoterminal telopeptide (NTX). Serum sex steroid concentrations did not associate with bone mineral content, scan area, or bone mineral density, adjusted for anthropometric and lifestyle factors at any measurement site. Instead, serum total (r = 0.23; P = 0.008) and free (r = 0.15; P = 0.023) T were positive predictors of serum TOC, whereas serum free E(2) correlated inversely with serum PINP (r = -0.20; P = 0.0039), TOC (r = -0.12; P = 0.086), COC (r = -0.14; P = 0.036), and urinary NTX (r = -0.15; P = 0.041). Interestingly, serum SHBG correlated positively with all the bone markers studied, the correlation coefficients being 0.18 for serum PINP (P = 0.012), 0.24 for TOC (P = 0.0006), 0.24 for COC (P = 0.0005), 0.27 for serum TRACP5b (P < 0.0001), and 0.21 for urine NTX (P = 0.0031). Serum SHBG was also a positive predictor of serum 25-hydroxyvitamin-D level (r = 0.20; P = 0.0036). The correlations of SHBG persisted after adjusting for weight, free E(2), and free T. We conclude that single measurements of serum E(2) and T were not determinants of peak bone mass in this population of young men. However, E(2) and T contributed to bone turnover rate, with serum T increasing bone formation, and serum E(2) suppressing both bone formation and resorption. Moreover, serum SHBG appeared to be an independent positive predictor of bone turnover rate, which also positively associated with serum 25-hydroxyvitamin-D levels.

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Nineteen men (29.2%) had vitamin D deficiency (25-OHDp20 nmol/l) and 48 men (73.8%) had hypovitaminosis D (25-OHDp37.5 nmol/l). Serum 25-OHD and iPTH levels correlated inversely (r ¼ À0.30; P ¼ 0.017). Serum 25-OHD levels were 52.0% higher for 13 vitamin D supplement users than for 51 non-users (P ¼ 0.0001). After exclusion of supplement users, an association between 25-OHD level and consumption of milk products was found (P ¼ 0.011), with the median vitamin D level being 6.5 nmol/l higher for those consuming four glasses of milk products or more daily than for those consuming one or less. Likewise, the higher the milk consumption, the higher the difference in 25-OHD between years 2004 and 2001 (P ¼ 0.0025). Conclusion: Vitamin D fortification of milk products slightly but insufficiently improved the poor vitamin D status of young Finnish men during winter. Further supplementation is warranted in order to normalize vitamin D levels and to support achievement of maximum peak bone mass.