Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.

ABSTRACT:We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 mg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean ± SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 ± 1.48% for teriparatide and 5.25 ± 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 ± 3.06% and 9.70 ± 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 ± 0.41% in the teriparatide and 4.14 ± 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino-terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (214%, p = 0.005) and 6 mo (219%, p < 0.001) and in serum b-C-terminal telopeptide of type I collagen (b-CTX) at 1 and 3 mo (211%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone-forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.

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ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months.DesignProspective, multinational, and observational study.MethodsData on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model.ResultsOf the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to <18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed.ConclusionsPostmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.

There is increased evidence that the dopaminergic system plays a major role in the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major inhibitory factor of prolactin release and also influences growth hormone (hGH) secretion. The aim of this study was to measure the endocrine activity of RLS patients, to compare it with that of normal subjects and to detect possibly altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and cortisol plasma levels were measured every 20 min for 24 hours in 10 male never-medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5 years). The blood samples taken during the night were paralleled by polysomnographic recordings including the assessment of periodic leg movements (PLM). Plasma levels as well as frequency and amplitude of the pulses of prolactin, hGH and cortisol were not different between RLS patients and controls. Both groups showed the same rhythms during the night- and daytime for all hormones. Cross correlations resulted in high correlation coefficients for each hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and prolactin, respectively). Concerning sleep parameters, there were no significant differences between the two groups apart from a higher PLMS arousal index in RLS patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It is suggested that a possible dysfunction of the dopaminergic system in RLS does not affect the release of prolactin and hGH from the pituitary gland.

Raloxifene treatment in postmenopausal women with osteoporosis was associated with a marked reduction of skeletal pain and analgesic consumption and an improvement in subjective sleep quality. Further investigation in a randomised, placebo-controlled trial is warranted.

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The treatment of osteoporotic patients with teriparatide is associated with a significant increase in bone formation and gain of bone mass. The purpose of this post hoc analysis was to determine if the cross-sectional area (CSA) of the spinal canal and the vertebral body is affected by teriparatide treatment. Narrowing of the spinal canal might represent a safety problem, while widening of the vertebral CSA might improve mechanical stability. High-resolution computed tomography (HRCT) scans of vertebra T12 were obtained at baseline and after 6, 12, and 24 months of teriparatide treatment (20 μg/day) from 44 postmenopausal women with established osteoporosis participating in the prospective, randomized EUROFORS study. The CSA of the spinal canal did not decrease but increased marginally by 0.9% (2.6 mm2) over 24 months (P < 0.001), with a range from −0.5% (−2 mm2) to 3.1% (+8 mm2). Even when analyzing the spinal CSA on a slice-by-slice basis, no clinically relevant narrowing of the spinal canal was observed. For vertebral bodies, the CSA increased by 0.7% (5.7 mm2) over 24 months (P < 0.001), with a range from −0.4% (–3 mm2) to 1.6% (+14 mm2). Our data do not provide evidence for safety concerns regarding spinal canal narrowing. On the other hand, the increases observed for vertebral CSA apparently also only minimally contribute to the mechanical strengthening of the vertebral body under teriparatide treatment.