Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide.

UNLABELLED: We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. INTRODUCTION: The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. METHODS: We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 µg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. RESULTS: Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. CONCLUSIONS: This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs.

Persistence with teriparatide in postmenopausal osteoporosis; impact of a patient education and follow-up program: the French experience.

SUMMARY: This study evaluated the 18-month persistence with teriparatide in 5413 postmenopausal osteoporotic women who were enrolled in an education and follow-up program. Analysis showed that the persistence rate was 81.5% for women who follow the program, higher than for existing oral antiresorptive treatments. INTRODUCTION: An education and follow-up program was developed after launch of teriparatide in France in September 2004, to help women to follow the treatment. The objective of this study was to evaluate the persistence with teriparatide in postmenopausal osteoporotic women following this program. METHODS: Data about persistence are available for the period September 2004 to June 2007. Persistence is defined as the percentage of patients still on treatment at the end of the 18-month course, and it has been compared to the data provided by the French universal health insurance system. RESULTS: Since the launch of teriparatide in France in September 2004, 5413 postmenopausal women (mean age 72.3 +/- 14.5 years) with osteoporosis and vertebral fractures (mean 3.9 +/- 2) have participated in the program. The persistence rate at 15 months was 81.5%, and our analysis suggested that a majority of patients completed the 18-month treatment course. The main reason for discontinuation was adverse events (46.7%). Data of the French Universal Health Insurance suggest that the persistence may be close to 0% for women who are not in the program. CONCLUSIONS: Postmenopausal osteoporotic women treated by teriparatide and enrolled in an education and follow-up program have a high persistence rate.

Inverse relationship between vertebral fractures and spine osteoarthritis in postmenopausal women with osteoporosis.

BACKGROUND: Although the coexistence of osteoarthritis and osteoporosis is considered as uncommon, it has been suggested that, in postmenopausal women, disc space narrowing increases the risk of vertebral fracture. The aim of this study was to check this hypothesis in postmenopausal women with osteoporosis. OBJECTIVE: We analysed the relationship between vertebral fractures and spine osteoarthritis in 410 postmenopausal women with osteoporosis: in this population both disc space narrowing and osteophytes are inversely related to vertebral fractures. PATIENTS AND METHODS: This study is based on baseline data collected in a multicentre, prospective and 6-month longitudinal observational study. 410 postmenopausal women (74+/-5 years) were enrolled who had consulted for back pain, and had osteoporosis (according to WHO definition). Spine x-rays were performed according to standardised procedures. Vertebral fractures were evaluated from T4 to L4 using the Genant's semiquantitative method; osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at all levels of the thoracic and lumbar spine, and by a qualitative assessment of facet joint arthritis. RESULTS: The prevalence of vertebral fractures was 52.4%. At least one osteophyte, one disc space narrowing and one facet arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse association between vertebral fractures and osteoarthritis: odds ratios adjusted for age and weight (95% CI) were 0.38 (0.17-0.86), p = 0.02 and 0.27 (0.16-0.46), p<10(-4) for the presence of at least one osteophyte, and of at least three disc space narrowings respectively. In a cluster analysis, it was possible to identify a subgroup of patients without any disc space narrowing, and another subgroup with all patients having at least one disc space narrowing; the proportion of patients having more than three vertebral fractures was 25.2 and 15.9% in these two clusters respectively. CONCLUSIONS: Disc space narrowing and osteophytes are associated with a decreased vertebral fracture prevalence in postmenopausal women with osteoporosis.

A clinical tool to determine the necessity of spine radiography in postmenopausal women with osteoporosis presenting with back pain.

BACKGROUND: Vertebral fractures are underdiagnosed, although the resulting mortality and morbidity in postmenopausal women with osteoporosis is now recognised. In a population of postmenopausal women with osteoporosis and back pain, symptoms may be related to vertebral fractures or degenerative changes of the spine. AIM: To evaluate a population of postmenopausal women presenting with back pain and factors associated with vertebral fractures which were assessable in a clinical setting in order to determine the necessity for spine radiography. METHODS: Patient questioning and physical examination were carried out and spinal radiographic data collected from 410 postmenopausal women with osteoporosis, with an average age of 74 years, who consulted a rheumatologist for back pain. Of these, 215 (52.4%) patients were diagnosed with at least one vertebral fracture. Logistic regression was used to identify the most relevant clinical features associated with existing vertebral fractures, and to derive a quantitative index of risk. RESULTS: The model included six parameters: age, back pain intensity, height loss, history of low trauma non-vertebral fractures, thoracic localisation of back pain and sudden occurrence of back pain. The scoring system, or the quantitative index, had a maximal score of 16. For a score >or=7, the probability of existing vertebral fracture was >or=43%. The correlation between this quantitative index and the logistic model probability was 0.98, suggesting an excellent and highly significant approximation of the original prediction equation. CONCLUSIONS: From six clinical items, an index was built to identify women with osteoporosis and back pain who should have spine radiography. This simple tool may help clinicians to optimise vertebral fracture diagnosis and to make a proper therapeutic decision.

[Results of international clinical trials with raloxifene]. / Résultats des études cliniques internationales du raloxifène.

A new drug class called Selective Estrogen Receptor Modulators (SERM) could combine ideal properties for a product designed for menopausal women. The most widely studied member of this class is raloxifene which is currently marketed in several countries for the prevention of osteoporosis in menopaused women. This product is a nonsteroidal derivative of benzothiophene which, like estrogens, has a preventive effect against bone loss involving the spine and peripheral skeleton and a cholesterol lowering effect, both in the ovariectomized rat and in menopausal women. Unlike estrogens, raloxifene does not stimulate breast or uterine tissue. These interesting properties make raloxifene a possible preventive treatment for osteoporosis and other menopause-related risks for menopausal women of all ages. Multicenter studies have been conducted in recently menopausal women who received either raloxifene at the doses of 30, 60, or 150 mg/day or a placebo in a randomized protocol. All subjects were also given calcium supplementation. Bone density was measured twice a year for 36 months by dual X-rays absorptiometry and showed a significant decrease at all sites in the placebo group while there was a significant increase in the spine, the hip and the overall skeleton for all three raloxifen groups. After 24 months of treatment, mean increase over placebo was 2.4% for 60 mg raloxifene measured on the spine and total hip and 2% for the overall skeleton. Markers of bone formation (serum osteocalcin and bone alkaline phasphatase) and resorption (urinary CrossLaps) decreased significantly reaching, after 3 to 6 months of treatment, the levels observed in non menopausal women. In addition, total serum cholesterol as well as LDL-cholesterol decreased significantly in a dose-dependent fashion in all groups treated with raloxifene. Serum HDL-cholesterol and triglycerides did not very significantly during treatment. Hot flashes were the most frequently observed undesirable effect, at a frequency slightly higher in the raloxifene group (25%) than in the placebo group (18%). This undesirable effect was of low intensity and generally occurred during the first months of treatment. It did not cause a higher drop out rate (raloxifen 1.5%; placebo 2.1%). The preliminary data at two years follow-up suggest that raloxifene is not associated with an increased risk of breast cancer. In conclusion, raloxifene is a particularly interesting drug for menopausal women showing very promising efficacy and clinical tolerance.

Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group.

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.