Springer Science and Business Media LLC

Teriparatide is a drug for the treatment of osteoporosis which is licensed for use for up to 24 months. There is little experience with retreatment. The aim of this study was to evaluate, in three patients with severe secondary osteoporosis, the response to a second cycle of teriparatide regarding bone mineral density (BMD) and osteocalcin. Case 1 : A 62-year-old woman with multiple vertebral fractures has received corticoids for a long time. After starting teriparatide, her BMD and osteocalcin increased. She then received ibandronate for 3 years but her BMD declined. After a second treatment with teriparatide, her BMD increased again (18%). Case 2 : A 60-year-old woman with severe osteoporosis in lumbar spine (LS) (T-score − 4.5) had received corticoids for a long time and had celiac disease. After starting teriparatide, her BMD improved by 11.7%. She then received zoledronic acid for 15 months, but bone density decreased, so she was retreated with teriparatide. BMD had a slightly higher increase than after the first cycle (12.6%). Case 3 : A 60-year-old woman consulted for osteoporosis (LS T-score − 5.3), several fractures, and hyperthyroidism. She started teriparatide with improvement in BMD (39%). After 24 months, she received ibandronate for 1 year, but as her BMD declined, she was retreated with teriparatide. BMD showed an increase of 15%. The indication of a second cycle of treatment with teriparatide in three patients was effective in increasing BMD. Additional studies are needed to further identify the benefits and safety of retreatment with teriparatide.

The relationship between spinal curvature and bone mineral density (BMD) in women was examined. Significant relationships were observed between spinal curvature and BMD in both pre- and postmenopausal women. Excessive spinal curvature may be associated with low bone mass in premenopausal women. The purpose of this study was to examine the associations between spinal measurements of thoracic and lumbar curvatures and bone mineral density in pre- and postmenopausal women. The data for this study were obtained from the Texas Woman’s University Pioneer Project. Female participants (n = 242; premenopausal n = 104, postmenopausal n = 138) between the ages of 18 and 60 years were evaluated on multiple health measures. Thoracic and lumbar curvatures were measured with a 24-in. (60 cm) flexicurve. Bone mineral density was assessed via dual-energy X-ray absorptiometry (Lunar DPX IQ, version 4.6e). Pearson correlations and logistic regression analysis were used to examine the associations between the obtained spinal curvature measurements and bone mineral density. Significance was set at p < .05. Significant correlations were observed for the femoral neck and lumbar spine bone mineral density with thoracic and lumbar curve in premenopausal women (r = −.344 to − .525; p < .001). Slightly weaker, but significant, correlations were observed for femoral neck and lumbar spine in relation to thoracic and lumbar curve in postmenopausal women (r = −.288 to −.397; p < .01). Premenopausal women with thoracic curvature greater than 4 cm had a greater risk of having low bone mass compared to premenopausal women with less than 4 cm of curvature (odds ratio = 3.982, 95 % CI = 1.206, 13.144). The observed negative relationship suggests that as either thoracic or lumbar curvature increases, the regional bone mineral density decreases in both pre- and postmenopausal women.

Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d.) or a matched placebo, according to a double-masked, parallel-group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while it decreased in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.

In postmenopausal women with low bone mass and hormone-receptor-positive breast cancer on an aromatase inhibitor, risedronate maintained skeletal health assessed by bone density and turnover markers. Women with the greatest decreases in bone turnover markers at 12 months had the greatest increases in bone density at 24 months. Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone-receptor-positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if (1) oral bisphosphonate therapy can prevent bone loss in women on an AI and (2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). We conducted a 2-year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an AI (anastrozole, letrozole, or exemestane) for hormone-receptor-positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo, and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)], and safety. Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p < 0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 μg/mL for P1NP (both p < 0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p < 0.05). The oral therapy was safe and well tolerated. In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health.

The effects of treatment with 100 μg parathyroid hormone (PTH) (1–84) or an identical placebo on muscle function and quality of life (QoL) was studied in hypoparathyroid patients. At baseline, we found reduced QoL but no myopathy in the patients. Six months of treatment did not improve QoL, and muscle strength decreased slightly. A reduced quality of life (QoL) and myopathy that may be due to the absence of PTH have been reported in patients with hypoparathyroidism (hypoPT). Sixty-two patients with chronic hypoPT were randomized to 6 months of treatment with either PTH(1–84) 100 μg/d s.c. or placebo, given as add-on therapy to conventional treatment. Muscle function and postural stability were investigated using a dynamometer chair, a stadiometer platform, the repeated chair stands test, the timed up and go test, and electromyography. QoL was assessed using the 36-item Short Form Health Survey and the WHO-5 Well-Being Index. The mean age of the patients was 52 ± 11 years, and 85 % were females. At baseline, QoL was significantly reduced in comparison with norm-based scores. Compared with placebo, PTH did not improve QoL or muscle function. Rather, max force production decreased significantly by 30 % at elbow flexion in the PTH group compared with the placebo group. Moreover, there was a nonsignificant trend for muscle strength to decrease in the upper extremities and on knee extension in response to PTH. Treatment did not affect postural stability. Electromyography showed a slight decrease in the duration of motor unit potentials in the PTH group, indicating a tendency toward myopathy, which, however was not symptomatic. Overall, our data do not support an immediate beneficial effect of PTH replacement therapy on muscle function or QoL. A high frequency of hypercalcemia among our patients may have compromised the potential beneficial effects of reversing the state of PTH insufficiency.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that can lead to local joint deformations (bone erosions and joint space narrowing) and to extra-articular phenomena, including generalized osteoporosis. In addition, in patients with RA, the risk of vertebral and nonvertebral fractures is doubled. High disease activity (inflammation), immobility, and glucocorticoid use are common factors that substantially increase fracture risk in these patients, on top of the background fracture risk based on classical risk factors such as high age, low body mass, and female gender. New insights on the links between the immune system and the bone system, the field of osteoimmunology, have shown that local and generalized bone loss share common pathways. The receptor activator of nuclear factor κB ligand/osteoprotegerin pathway (RANKl/OPG) is one of the most important pathways, as it is (strongly) upregulated by inflammation. In modern treatment of RA with biologics, for example, TNFα-blocking agents and combination therapy of conventional disease-modifying antirheumatic drugs (DMARDs), clinical remission is a realistic treatment goal. As a consequence, in recent studies, it has been documented that both local and generalized bone loss is absent or minimal in those patients who are in clinical remission.

Vitamin D, parathyroid hormone levels and calcium absorption was assessed before and after cholecalciferol using Strontium as a surrogate. Increase in 25OHD, lowering of iPTH with no effect on Sr absorption was seen, suggesting the possibility that maximal Ca absorption had already been achieved in these volunteers. This paper discusses the determination of calcium (Ca) absorption, using strontium (Sr) as a surrogate, before and after a single IM injection of vitamin D3 (600,000 IU). Baseline serum 25-hydroxyvitamin D (25OHD), Sr, Ca, P, and intact parathyroid hormone (iPTH) were determined in 53 fasting volunteers, followed by administrating (PO) 0.03 mM (4.8 mg/kg) SrCl2 and collecting blood at 0.5, 1 and 4 h to determine the absorption (AUC0→t ) of Sr. Following the initial absorption test, volunteers received a single IM injection of 600,000 IU vitamin D3. Two months later, the fasting serum and the Sr absorption test were repeated, as described above. The IM injection of vitamin D3 caused a significant increase in fasting 25OHD (from 43.5 ± 19 to 66.1 ± 19.1 nmol/L (p < 0.001)) and a trend toward lower serum iPTH (from 59.8 ± 27.8 to 53 ± 31 ng/L). Fasting serum Ca and P remained unchanged. A higher 25OHD level failed (p = 0.32) to translate into a higher rate of Sr absorption. AUC0→4 h were almost identical before and after the IM injection of vitamin D3. A single vitamin D3 injection of 600,000 IU significantly increase mean 25OHD concentration and tended to lower iPTH concentrations in volunteers with initially low 25OHD status, suggesting to utilize this simple form of treatment to improve vitamin D status and to have a possible biological effect on Ca homeostasis. However, we found no obvious effect on Sr absorption, suggesting the possibility that maximal vitamin D-dependent Ca absorption had already been achieved in these volunteers at a lower vitamin D status.

Osteocalcin is a major component of bone matrix. Concentrations of total, carboxylated, and uncarboxylated osteocalcin, are highly heritable and genetically correlated with bone mineral content (BMC) within African ancestry families. Osteocalcin (OC) is a protein constituent of bone matrix and a marker of bone formation. We characterized the heritability of serum OC measures and identified genomic regions potentially involved in the regulation of OC via high-density genome-wide linkage analysis in African ancestry individuals. African ancestry individuals (n = 459) were recruited, without regard to health status, from seven probands (mean family size = 66; 4,373 relative pairs). Residual heritability of serum OC measures was estimated and multipoint quantitative trait linkage analysis was performed using pedigree-based maximum likelihood methods. Residual heritabilities of total OC, uncarboxylated OC, carboxylated OC and percent uncarboxylated OC were 0.74 ± 0.10, 0.89 ± 0.08, 0.46 ± 0.10 and 0.41 ± 0.09, respectively. All OC measures were genetically correlated with whole body BMC. We obtained strong evidence of bivariate linkage for percent uncarboxylated OC and whole body BMC on chromosome 17 (logarithm of the odds [LOD] = 3.15, 99 cM). All forms of OC were highly heritable and genetically correlated with total body BMC in these African ancestry families. The identified linkage region contains several candidate genes for bone and energy metabolism including COL1A1 and TNFRSF11A. Further studies of this genomic region may reveal novel insight into the genetic regulation of OC and bone mineralization.