Bone Mass Gain Research Articles

Adiposity and TV Viewing Are Related to Less Bone Accrual in Young Children

To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospectively for 4 years, with a focus on the role of physical activity and TV viewing. Children were part of a longitudinal study in which measures of fat, lean and bone mass, height, weight, activity, and diet were taken every 4 months from ages 3 to 7 years. Activity was measured by accelerometer and TV viewing by parent checklist. We included 214 children with total body dual energy x-ray absorptiometry (Hologic 4500A) scans at ages 3.5 and 7 years. Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 years (P < .001). More TV viewing was related to smaller gains in bone area and bone mass accounting for race, sex, and height. Activity by accelerometer was not associated with bone gains. Adiposity and TV viewing are related to less bone accrual in preschoolers.

Behandlung der primären Osteoporose mit Calcium und Lachscalcitonin

Fifty-nine consecutive patients (19 men, 40 women, mean age 60.8 [27-80] years) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin. All the patients were given 1 g calcium by mouth every morning. Group 1 (n = 20) received no other specific medication while group 2 (n = 19) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 (n = 20) received the same dose every evening. The pain reported by the patients was subdivided into four severity grades, and analgesic consumption was recorded. In group 1 there was a nonsignificant decrease in pain, but in groups 2 and 3 there was a highly significant diminution in pain (P less than 0.005) and in analgesic intake (P less than 0.01). Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5% increase in the distal radius in group 2 (P = 0.0001) and a 7.1% increase in group 3 (P = 0.0001), while in group 1 mineral content had decreased by 4.3% (nonsignificant). These results show that a significant gain in bone mass can be achieved by administration of calcitonin, either daily or on alternate days. The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1.

A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management

To review outcome measures and treatment costs in children with juvenile idiopathic arthritis (JIA) and low bone mineral density (BMD) and/or fragility fractures. To review evidence for effectiveness and safety of bisphosphonates and calcium and/or vitamin D in these children. To assess long-term bone health in adults with JIA. Major databases were searched up to July 2005 for effectiveness studies and up to January 2005 for costs. A structured search strategy was conducted. For the evaluation of long-term bone health, outcome data were derived from two cohorts of adult patients with JIA. As there were few published cost data, an ongoing UK longitudinal study (CAPS) provided background data on the cost of managing JIA. Sixteen studies (78 children with JIA) were included. At baseline, the children had BMD below the expected values for age- and sex-matched children; treatment with bisphosphonates increased BMD with mean percentage increases in spine BMD varying from 4.5 to 19.1%. None of the studies with control groups compared results between the intervention and control groups, they only compared each group with its own baseline. Overall, studies were heterogeneous in design, of variable quality and with no consistency in methods of assessing and reporting outcomes. Hence, data could not be combined or an effect size calculated. A further 43 papers were included in the safety review; side-effects were generally transient. Two studies assessed treatment with calcium and/or vitamin D; BMD was increased from 0.75 to 0.830 g/cm2 after 6 months and BMD Z-score from -2.8 to -2.3 after 6 months and -2.4 after 1 year. There are relatively few long-term studies on the occurrence of low BMD and fragility fractures in children with JIA, with most studies only following children for 1 or 2 years. However, the long- and short-term data indicate that children with JIA have a lower BMD and more fractures than children without JIA. There are very few data on long-term bone health from adults who have JIA, but studies indicate that low BMD persists into adulthood, although adults in remission from JIA may attain the same BMD as healthy adults. From the available data, any predictors of low BMD and fractures in children and adults with JIA remain uncertain. No studies were found that discussed the costs of treating children with JIA and low BMD and/or fragility fractures. In CAPS, 297 of 457 children with JIA attended a 12-month follow-up visit. The mean annual total cost per child in the first year after diagnosis was 1649 pounds (standard deviation 1093 pounds, range 401-6967 pounds). The highest cost component was appointments with paediatric rheumatologists. The study is continuing to accrue and follow up patients and further analyses will be undertaken as the study progresses. BMD, adjusted for size, should be assessed as the primary outcome in studies of bone health in children with JIA. Quantitative computed tomography could be used where equipment is available as it offers the advantage of measuring volumetric density. Bisphosphonates are a promising treatment for osteoporosis in children with JIA, but the quality of the current evidence is poor. The accurate assessment of outcome is crucial. There are still uncertainties about the use of bisphosphonates in children, including whether the positive effects of treatment continue over time, the length of treatment and the maximal bone mass gain that can be achieved. Adults with JIA may have persistent low BMD compared with an otherwise healthy population together with an increased risk of fracture. There are no studies evaluating the costs of treating children with JIA and low BMD and/or fragility fractures. There are few data evaluating the costs of treating JIA in general. In the first 12 months after diagnosis, children with all JIA disease subtypes consume large, but highly variable, quantities of health service resources, the largest component being the consultant rheumatology appointments. Data from a larger cohort, over a longer period, are required to substantiate these results further. Further research is needed to assess more clearly the role and permit licensing of bisphosphonates for treatment of children, and in particular, longer-term studies.

Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.

Hiperparatiroidismo primario. Papel actual de la densitometría ósea

To describe the usefulness of bone densitometry in the diagnosis and follow-up of patients with primary hyperthyroidism (PHPT). Retrospective review of 48 patients with PHPT; 27 received surgical treatment and 21 medical treatment. Radiologic and biochemical findings and bone mass were evaluated at the start of the study and after one and two years. All patients had elevated PTH levels and 87% had normal or moderately increased calcemia. The most common clinical presentations were renal colic (34%) and the absence of symptoms (22.8%). The sensitivity of scintigraphy was 75% and the sensitivity of ultrasonography was 12%. We found osteopenia in 70.3% of patients and osteoporosis in 81.3%, fundamentally in the radius and spine. Bone mass at one year and at two years remained similar in the femur (73.8%) and spine (81.8%) in 58% and 50% of the patients, respectively. Increased bone mass was seen in the femur (30.4%) in 13.6% of the patients and in the spine (33.3%) in 50% of the patients. This increase was greater in the group that received surgical treatment. Calcemia and PTH were decreased by 69.2% and 76.9 %, respectively, in the patients that underwent surgery. In the group that received medical treatment, calcemia remained similar and PTH was decreased by 50%. Fractures developed in 21.8% of the patients. Densitometry assesses the repercussions of the disease on bone mass at the start of treatment and after treatment. Osteoporosis is a common finding. Gains in bone mass occurred fundamentally in patients that had undergone surgery. Bone mass remained similar in a high percentage of patients in both groups.

Beneficial Effects of Combined Administration of Alendronate and Alfacalcidol on Cancellous Bone Mass of the Tibia in Orchidectomized Rats: A Bone Histomorphometry Study

The purpose of the present study was to examine the effects of combined administration of alendronate (ALN) and alfacalcidol (ALF) on the cancellous and cortical bone mass of the tibia in orchidectomized rats. Fifty male Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into five groups: age-matched control, orchidectomy, and orchidectomy with administration of ALN (2.5 mug/kg, s.c., 5 times a week), ALF (0.05 microg/kg, p.o., 5 times a week), or ALN+ALF. The total experimental period was 12 wk. Orchidectomy reduced the cancellous bone mass of the proximal tibial metaphysis and maturation-related cortical bone gain of the tibial diaphysis as a result of increased trabecular bone resorption and decreased periosteal bone formation and also increased endocortical bone erosion and formation. ALN suppressed trabecular bone resorption and endocortical bone erosion and formation and increased periosteal bone formation, while ALF increased the number of osteoblasts and suppressed trabecular bone resorption and markedly increased periosteal and endocortical bone formation. Thus, both ALN and ALF prevented the orchidectomy-induced reduction in the cancellous bone mass and maturation-related cortical bone gain. Combined administration of ALN and ALF increased the cancellous bone mass as compared with the values observed in age-matched controls by causing more marked suppression of trabecular bone resorption. The present study showed the beneficial effects of combined administration of ALN and ALF on the cancellous bone mass of the tibia in orchidectomized rats.

Impaired Bone Health in Adolescents After Liver Transplantation

Long-term complications related to immunosuppressive medication are an important problem after liver transplantation (OLT). This study was carried out to evaluate the bone health and risk factors for osteoporosis and fractures in 40 pediatric liver transplant recipients. The results of 208 longitudinal bone mineral density (BMD) measurements were analyzed retrospectively. In addition, a dual-energy X-ray absorptiometry was performed to assess the bone mineral content more precisely and to detect subclinical vertebral fractures (VF). The median age of the patients was 14 years and mean postoperative follow-up 7.0 years. The results showed that over half (58%) had lumbar spine (LS) Z-score </=-1.0 and one-fifth (18%) had asymptomatic VF. LS Z-score tended to increase from the first year after OLT, but during puberty the bone mass gain was suboptimal and Z-scores decreased in some subjects. Patients with VF were older at the time of OLT (p = 0.002) and their LS Z-score was lower (p = 0.001). Children transplanted before 10 years of age had less VF (p = 0.004) and higher LS Z-score (p = 0.005) than older patients. In conclusion, adolescent liver recipients are prone to osteoporosis and prevention should be targeted especially to this age group.

Angiogenesis inhibitor attenuates parathyroid hormone-induced anabolic effect

In vivo osteogenic responses to anabolic stimuli are expected to be accompanied by angiogenesis as well as in the process of remodeling of bone. Consequently, angiogenesis might play an important role in mediating bone forming stimulating effect of parathyroid hormone (PTH). To investigate this relationship, we used actively growing young Sprague–Dawley rats and CKD-732, one of the angiogenesis inhibitor (AI) to reveal the relationship of angiogenesis in the effect of PTH. The groups were divided as (1) vehicle [VEH group], (2) PTH(1–84) [PTH group], (3) AI alone [AI group], (4) PTH(1–84) + AI concomitance [PTH-AI group] and were treated for 6 weeks. The bone mineral density (BMD) of PTH group was higher than VEH group and the gain of bone mass was attenuated in PTH-AI group. The maximal failure load in PTH group was higher than VEH group, but it was definitely attenuated by concurrent use of AI. Moreover, the toughness showed similar significant deterioration in PTH-AI group. General bone turnover was also significantly decreased in PTH-AI group as shown by the absence of increase in osteocalcin and β-crosslaps and by decrease in metaphyseal length. The BMD or the biomechanic data of AI only group were similar to the VEH group, suggesting the minimal effect of AI itself on the normal modeling phase of the growing rats. In conclusion, the angiogenesis seemed to contribute to completing the anabolic effect of PTH especially for bone strength.

Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report

IntroductionThe natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT).Case presentationA 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain.ConclusionThis case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.

Bone Mass in Prepubertal Boys Is Associated with a Gln223Arg Amino Acid Substitution in the Leptin Receptor

The contribution of leptin to bone mass acquisition in humans remains unclear. We investigated the association of the Gln223Arg polymorphism in the leptin receptor gene (LEPR) with bone mineral content (BMC) and areal bone mineral density (aBMD) in prepubertal boys and LEPR interaction with vitamin D receptor (VDR) genotypes (Bsm1 and Fok1). In a cross-sectional design with a longitudinal follow-up, dual-energy x-ray absorptiometry measurements at the lumbar spine, hip, femoral diaphysis, and radius were performed at baseline (mean age 7.4 +/- 0.4 yr) and 2 yr later in 222 healthy Caucasian males. LEPR genotypes were significantly associated with baseline BMC at the hip (P = 0.017), femur diaphysis (P = 0.019), and radius (P = 0.007) and with height (P = 0.041) as well as with physical activity (P = 0.016). Associations with height and BMC at femur diaphysis and radius remained significant after 2 yr. Significant differences in 2-yr bone mass gain at the spine and femur neck were also found among LEPR genotypes. In contrast, adjusting BMC for projected bone area (aBMD) and/or weight, height, and physical activity resulted in a weak association only at the femur (P = 0.014-0.054). VDR polymorphisms were not associated with BMC or aBMD, but significant interactions occurred between VDR Fok1 and LEPR genotypes. The LEPR Gln223Arg polymorphism was associated with bone mass in growing boys. The association, however, was markedly dependent on bone area, body size, and physical activity, in addition to VDR genetic variation, suggesting that the leptin system may modulate bone mass in humans mostly through indirect mechanisms.

Bone mass accretion rates in pre‐ and early‐pubertal South African black and white children in relation to habitual physical activity and dietary calcium intakes

To examine bone mass changes in 321 black and white South African children in relation to habitual physical activity (PA) levels and calcium intakes. Children underwent two bone mass scans at ages nine and 10 years using dual X-Ray absorptiometry. PA levels and calcium intakes were assessed using questionnaires. Data were analyzed by regressing change in bone mineral content (BMC) and bone area (BA) from age nine to 10, against BA (for BMC), height and body weight. The residuals were saved and called residualized BMCGAIN and BAGAIN. Residualized values provide good indication of weight, height and BA-matched accumulation rates. White children had significantly higher PA levels and calcium intakes than black children. Most active white males had significantly higher residualized BMCGAIN and BAGAIN at the whole body, hip and spine but not at the radius, than those who were less active. Most active white females had significantly higher residualized BAGAIN at all sites except the radius than less-active girls. No such effects were seen in black children. There was no interactive effect on residualized BMCGAIN for calcium intake and PA (except at the spine in white girls). Bone mass and area gain is accentuated in pre- and early-pubertal children with highest levels of habitual physical activity. Limited evidence of an effect of dietary calcium intakes on BMC was found.

Dietary protein intakes and bone growth

Peak bone mass is a significant determinant of fracture risk later in life. Nutritional intakes, particularly proteins, are able to modulate the genetic potential, with effects starting as early as in utero. There is a positive correlation between yearly lumbar and femoral bone mass gain, and protein intake. Dairy products consumption positively influences bone mineral density at the spine, hip and forearm in adolescents, leading thereby to a higher peak bone mass. Nutritional intakes, particularly proteins, are associated to bone growth, hence to bone strength and resistance to fracture later in life. The growth hormone IGF-I-target organ axis is likely to be implicated in this process. Variations in the protein intake within the “normal” range can have a significant effect on skeletal growth and thereby modulate the genetic potential in peak bone mass attainment.

Impairment of bone mass development in children with chronic cholestatic liver disease

To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF-1 levels in children with chronic cholestatic disease (CCLD). A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7.2 +/- 4.8 years) and 22 control subjects (mean age 7.6 +/- 4.5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25-hydroxyvitamin D, PTH and IGF-1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient. Z-score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0.107 +/- 0.02 vs. CCLD = 0.092 +/- 0.02 g/cm(3), P < 0.05) and after conversion for bone age. All participants showed normal 25-hydroxyvitamin D levels, with no significant differences in serum levels of 25-hydroxyvitamin D and PTH between groups. IGF-1 levels were significantly lower in the CCLD group (control = 19.6 +/- 16.8 vs. CCLD = 6.4 +/- 7.6 nmol/l, P < 0.05) and a positive correlation was observed between whole body BMD and IGF-1 in this group. These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF-1 production might be responsible, at least in part, for the low bone mass of these patients.

Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass

Glucose-dependent insulinotropic peptide (GIP) is an intestinally secreted hormone the release of which is stimulated by nutrient ingestion. We previously reported that GIP receptors are present in osteoblastic cells and that GIP increases collagen type I synthesis and alkaline phosphatase activity in isolated osteoblasts. We have also shown that osteoclasts express GIP receptors and that GIP inhibits osteoclastic activity and differentiation. In addition, using GIP receptor knockout mice we demonstrated that absence of GIP receptor signaling resulted in a low bone mass phenotype. To further define GIP's role as an anabolic hormone in vivo, we utilized a genetically altered mouse model, a transgenic mouse overexpressing GIP under the control of the metallothionein promoter (Tg+). Tg+ mice had significantly higher mean GIP levels even in the absence of added dietary zinc. Tg+ animals also had a significant increase in markers of bone formation and a decrease in markers of bone resorption. Consistent with these biochemical data, GIP transgenic mice had a significant increase in bone mass as measured by densitometry and histomorphometry. These data support the conclusion that GIP inhibits bone resorption and stimulates bone formation and that excess signaling through the GIP receptor results in gain of bone mass. In view of GIP's role in nutrient absorption, our data suggest that this hormone may serve an important role in linking nutrient ingestion to bone formation.

Childhood Fractures Are Associated With Decreased Bone Mass Gain During Puberty: An Early Marker of Persistent Bone Fragility?

Childhood Fractures Are Associated With Decreased Bone Mass Gain During Puberty: An Early Marker of Persistent Bone Fragility?

Effects of Combined Treatment with Alendronate and Alfacalcidol on Bone Mineral Density and Bone Turnover in Postmenopausal Osteoporosis: A two-years, randomized, multiarm, controlled trial

One hundred ninety seven postmenopausal women with osteoporosis were enrolled in a prospective, randomized, single-blind, controlled trial of 24 months' duration to compare the efficacy of Alendronate 10mg + Alfacalcidol 0.5μg + 500 mg calcium (group A), Alendronate 10mg + 500 mg Calcium (group B), Alfacalcidol 0.5 μg + 500mg calcium (group C), or Calcium 500 mg (group D), on bone mineral density and bone metabolism markers. Upon inclusion, the subjects were randomized to groups A, B, C and D according to a 1.5/2/1.5/1 scheme. BMD was measured at the lumbar spine (L2-L4) and the femur neck using dual energy x-ray absorptiometry (LUNAR DPX) at baseline and after 12 and 24 months. Biochemical markers of bone metabolism including osteocalcin, urinary calcium and urinary deoxypyridinoline, were collected at baseline, 6 month, 12 month, and 24 month. Data collection and statistical analyses were performed in a single-blind fashion. SPSS 10.0 and Statistica 7.0 statistical packages were used for data encoding and analysis. The 5% level was used as threshold for statistical significance. Upon inclusion and randomization, patients' characteristics (age, height, weight, time since menopause,) and study outcomes (osteocalcin, urinary calcium, deoxypyridinoline, and BMD values) were homogeneous between the four groups. At 2-years, and at the lumbar level, the highest significant gain in bone mass was seen for group A (+8.4%), followed by group B (+6.4%), and group C (+2.3%), while a significant decrease was seen among subjects from group D (-2.5%). A similar pattern was observed at the femoral neck level, with gains ranging from +5.3% for group A, +3.8% for group B, +1.2% (NS) for group C, and -6.4% for group D. Significant reductions of osteocalcin levels were observed among groups A (-4 %), B (-5.7%), and C (-1.7%). Urinary calcium was significantly increased in group C (+14%), while decreased in group B (-5.6%). Deoxypyridinoline significantly decreased among verum groups (A: -68%, B: -63.3%, C: -45%) and increased in the control group (+18.1%). Intergroup differences revealed a significantly higher gain in bone mass induced by treatments regimen A, B and C compared to D at both the femoral and lumbar levels, a higher decrease of osteocalcin levels in groups A and B versus D, similar variations of urinary calcium among the four groups, and a significantly higher reduction in deoxypyridinoline in group A, followed by B and C, versus D. The incidence of increased 24 h urinary calcaemia was similar between the four groups (p>0.06). No case of clinical hypercalciuria or hypercalcemia has been recorded. Gastrointestinal side effects occurred in 4 patients in Group A, and in 5 patients in Group B, which resulted in the termination of treatment. Data from this randomized controlled trial suggested a higher efficacy in increasing bone mineral density and a similar tolerance of combined therapy with Alendronate and Alfacalcidol compared to Alfacalcidol alone, and to Alendronate as a consistent trend. Importantly, the combined therapy resulted in lower rates of hypercalciuria, hypercalcemia, and hypocalcemia compared to monotherapies.

Fluoxetine treatment increases trabecular bone formation in mice

Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (microCT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass.

Bisphosphonate therapy for osteoporosis and bone strength

Bisphosphonates are now the most widely used drugs for osteoporosis. When bisphosphonate is given, the response varies directly with the rate of bone turnover at baseline. In high turnover osteoporosis there could be a gain in bone mass, but it reach a plateau after 2 to 3 years. In normal or low turnover osteoporosis bone mass is stabilized or slightly increased. The best indication of bisphosphonate use for osteoporosis is high turnover. In high turnover osteoporosis bisphosphonate therapy is effective in increasing the stiffness and the toughness (bone strength) by increasing the mean degree of mineralization of bone tissue through the prolongation of secondary mineralization. But the long-term use of bisphosphonate would result in highly mineralized bone and disturbed repair of microcracks by inhibition of bone remodeling. Intermittent use of bisphosphonate could be recommended to avoid the deterioration of bone quality.

Low bone mass in children and adolescents

Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence.

Prediction of bone mass gain by bone turnover parameters after parathyroidectomy for primary hyperparathyroidism: neural network software statistical analysis

Primary hyperparathyroidism (pHPT) is the most frequent endocrine hypersecretion disease, and parathyroidectomy is the only curative option, since pharmacologic therapy reduces hypercalcemia but does not impede parathyroid hormone hypersecretion. According to guidelines from the National Institutes of Health, parathyroidectomy is associated with bone mass increase in some asymptomatic patients, while in others bone mass is not changed after surgery. Therefore, we performed the present study in an attempt to elucidate whether a preoperative biochemical bone parameter can be predictive of a significant vertebral bone mass increase in patients with pHPT. For each patient we analyzed the following preoperative parameters: parathyroid hormone, urinary calcium excretion, urinary type I collagen cross-linked N-telopeptide (NTX), osteocalcin, and vertebral computerized bone mineralography. All patients underwent vertebral computerized bone mineralography 12 months after the operation. Statistical analysis was carried out by a neural network program, an event-predicting software modeled on human brain neuronal connections, which is able to examine independent statistical parameters. The patients presenting with high preoperative bone turnover (especially high NTX levels) will have a 5% vertebral bone mass gain in 83.33% of cases after surgery, independently of the National Institutes of Health guidelines. A high preoperative NTX level seems to be the best predictor parameter for postoperative vertebral bone mass gain in patients with pHPT. Our study also illustrates that neural network software may be a valuable method to help elucidate which pHPT patients should undergo surgical treatment.