This study investigated the effects of a single administration of teriparatide on bone turnover markers in postmenopausal women. Teriparatide caused a transient increase in bone resorption and inhibition of bone formation followed by a subsequent increase in bone formation and a decrease in resorption that lasted at least 1 week.
This study aims to investigate the effects of a single subcutaneous administration of teriparatide on bone turnover markers to elucidate why once weekly intermittent administration of teriparatide is effective on osteoporosis.
Pharmacokinetics and calcium metabolism and bone turnover parameters were measured in 30 postmenopausal women after two doses of teriparatide (28.2 or 56.5 μg injection) or placebo in a randomized, double-blind, placebo-controlled study.
Teriparatide plasma concentration increased in a dose-dependent manner, and the maximum concentration was achieved 1 h after injection. Serum levels of calcium and phosphorus were transiently increased and decreased after teriparatide injection, respectively. Calcium metabolism returned to baseline levels 24 h later. Two days after injection, the serum level of 1,25-dihydroxy vitamin D was increased by ~80 % from baseline for both doses of teriparatide. Serum levels of osteocalcin and procollagen type I N-terminal propeptide decreased during the first 24 h followed by a ~10 % increase for 14 days. The serum level of cross-linked N-telopeptide (NTX) of type I collagen increased during the first 24 h followed by a 10 to 12 % dose-dependent suppression from baseline for 14 days. Urinary cross-linked C-telopeptide of type I collagen changes occurred in the same direction as serum NTX, but not dose dependently.
A single administration of teriparatide caused an immediate, transient increase in bone resorption and inhibited bone formation followed by an increase in bone formation and decrease in resorption for ≥1 week. These findings may provide proof for the effect of a once-weekly regimen of teriparatide on bone turnover.
Bone formation; Bone resorption; Bone turnover marker; Human; Single administration; Teriparatide
Teriparatide [rhPTH (1-34)] is an effective treatment for osteoporosis administered by daily subcutaneous injection. The objective of this study was to determine how much benefit women expect teriparatide to confer before agreeing to perform daily injections.
We recruited postmenopausal women who had recently undergone bone densitometry and were found to have either a T score less than −2.5 at the hip or spine and/or had a Fracture Index (FI) of ≥ 6. Participants completed an Adaptive Conjoint Analysis questionnaire to determine their treatment preferences.
The study sample included 185 women, mean age 71 (range 46 to 90). An increasing number of subjects preferred rhPTH (1-34) as the efficacy of teriparatide increased, but most women demanded efficacy advantages greater than those demonstrated in clinical studies. We found no association between absolute fracture risk and preference for rhPTH (1-34); however, subjects with an excessively high perceived risk of future fracture were more likely to accept daily subcutaneous injections compared to subjects with a lower perceived risk of future fracture (40% versus 15%, p=0.001).
Our results suggest that most women demand benefits far greater than those conferred by rhPTH (1-34) in order to administer daily subcutaneous injections to decrease their future risk of fractures.
Given the poor adherence for treatment of osteoporosis, and the choices older adults must make when paying for medications, development of novel treatment approaches should be based on older adults' treatment preferences.
Osteoporosis; Bisphosphonates; Recombinant Human Parathyroid Hormone; Decision-Making
Osteoporosis that is by far the most common metabolic bone disease, has been defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Anabolic therapy with teriparatide, recombinant human parathyroid hormone (PTH 1-34), stimulates bone formation and resorption and improves trabecular and cortical microarchitecture. Teriparatide is indicated for the treatment of men and postmenopausal women with osteoporosis who are at high risk for fracture, including those who have failed or are intolerant of previous osteoporosis therapy. In conclusion, although teriparatide seems quite effective in the treatment of osteoporosis, it may cause life-threatening hypercalcemia. Therefore, patients should be closely monitored if symptoms of hypercalcemia are present during teriparatide treatment. Sustained hypercalcemia due to teriparatide treatment can not be seen in literature so we wanted to emphasize that severe hypercalcemia may develop due to teriperatide.
Hypercalcemia; osteoporosis; teriparatide
Osteoanabolic therapy is an attractive therapeutic option for men with osteoporosis because it directly stimulates bone formation, an action not shared by any antiresorptive drug. Teriparatide (recombinant human PTH(1-34)) and PTH(1-84) are available in many countries but PTH(1-84) is not available in the United States. Only teriparatide is approved for the treatment of osteoporosis in men. It is also indicated in glucocorticoid-induced osteoporosis. Teriparatide is associated with major gains in bone density at the lumbar spine and, to a lesser extent, in the hip regions. Vertebral and nonvertebral fractures are reduced in postmenopausal women treated with teriparatide. Fracture reduction data in men are less secure because the number of study subjects is small and the studies have not been powered to document this endpoint. Nevertheless, observational data in men suggest a reduction in vertebral fractures with teriparatide. Attempts to show further beneficial effects of teriparatide in combination with antiresorptive agents have not been demonstrated yet to be superior to monotherapy with teriparatide alone. The duration of therapy with teriparatide is limited to 2 years. Thereafter, it is necessary to treat with an antiresorptive drug to maintain, and perhaps increase, densitometric gains. Teriparatide is well tolerated with a good safety profile.
In this observational study in postmenopausal women with severe osteoporosis, the incidence of fractures was decreased during 18 months of teriparatide treatment with no evidence of further change in the subsequent 18-month post-teriparatide period when most patients took other osteoporosis medications. Fracture reduction was accompanied by reductions in back pain.
To describe fracture outcomes and back pain in postmenopausal women with severe osteoporosis during 18 months of teriparatide treatment and 18 months post-teriparatide in normal clinical practice.
The European Forsteo Observational Study (EFOS) was a prospective, multinational, observational study. Data on incident clinical fractures and back pain (100 mm Visual Analogue Scale [VAS] and questionnaire) were collected. Fracture data were summarised in 6-month intervals and analysed using logistic regression with repeated measures. Changes from baseline in back pain VAS were analysed using a repeated measures model.
A total of 208 (13.2%) of 1,576 patients sustained 258 fractures during 36 months of follow-up: 34% were clinical vertebral fractures and 66% non-vertebral fractures. The adjusted odds of fracture were reduced during teriparatide treatment and there was no evidence of further change in the 18-month post-teriparatide period, during which 63.3% patients took bisphosphonates. A 74% decrease in the adjusted odds of fracture in the 30- to <36-month period compared with the first 6-month period was observed (p < 0.001). Back pain decreased during teriparatide treatment and this decrease was sustained after teriparatide discontinuation. Adjusted mean back pain VAS decreased by 26.3 mm after 36 months (p < 0.001) from baseline mean of 57.8 mm.
In a real-life clinical setting, the risk of fracture decreased during teriparatide treatment, with no evidence of further change after teriparatide was discontinued. The changes in back pain seen during treatment were maintained for at least 18 months after teriparatide discontinuation. These results should be interpreted in the context of the design of an observational study.
Electronic supplementary material
The online version of this article (doi:10.1007/s00198-010-1498-5) contains supplementary material, which is available to authorized users.
Back pain; Fracture; Osteoporosis; Teriparatide
Recombinant human parathyroid hormone (1–34) (rhPTH 1–34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis. The mechanisms of action include a pulsative influence on the RANKL/OPG system resulting in osteoblast activation and increased bone formation by teriparatide. In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others. We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.
As the population ages, the burden of osteoporosis in men is expected to rise. Implementation of preventive measures such as falls prevention strategies, exercise and adequate calcium and vitamin D intake is recommended. However, when the diagnosis of osteoporosis is made, effective treatments need to be initiated to prevent fractures. As opposed to postmenopausal women, reduced bone formation is the predominant mechanism of age-related bone loss in men, making anabolic agents a logical treatment option for men with osteoporosis. Teriparatide is the only anabolic agent currently approved for treatment of osteoporosis in men. This paper summarizes the mechanism of action of teriparatide, as well as its tolerability and safety. Furthermore, the evidence supporting the efficacy of teriparatide treatment in men with osteoporosis is reviewed and its current role in the management of osteoporosis in men is discussed.
osteoporosis; pathophysiology; treatment; parathyroid hormone; men
We describe here the case of an elderly female with severe osteoporosis, who presented with a worsening backache, following teriparatide treatment. She was subsequently diagnosed to have normocalcemic primary hyperparathyroidism. Before prescribing teriparatide, an appropriate endocrine evaluation must be undertaken by all healthcare physicians (serum intact parathyroid hormone (iPTH) level), despite having a normal serum calcium. Normocalcemic hyperparathyroidism should be considered as an important alternate cause for osteoporosis.
Forsteo; hyperparathyroidism; normocalcemic hyperparathyroidism; osteoporosis; parathyroid adenoma; teriparatide
The Osteosarcoma Surveillance Study, an ongoing 15-year surveillance study initiated in 2003, is a postmarketing commitment to the United States (US) Food and Drug Administration to evaluate a potential association between teriparatide, rhPTH(1–34), a recombinant human parathyroid hormone analog (self-injectable medication to treat osteoporosis), and development of osteosarcoma in response to a finding from preclinical (animal) studies. Incident cases of primary osteosarcoma diagnosed in adults (aged ≥40 years) on or after January 1, 2003, are identified through population-based state, regional, and comprehensive cancer center registries in the US. Information on possible prior treatment with teriparatide, on demographics, and on risk factors is ascertained by patient or proxy telephone interview after patient consent. Between June 2004 and September 30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating cancer registries (estimated to be 62% of all adult cases in the US for that time period); 549 patients or proxies were interviewed. Interviewed patients were similar to noninterviewed patients with regard to mean age, sex, race, and geographical distribution and tumor type and site of tumor. Mean age of those interviewed was 61 years, 46% were female, 86% were white, and 77% were alive when the case was reported to the study investigators. Data collected in the study provide descriptive information on a large number of adults with osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there were no osteosarcoma patients who had a prior history of teriparatide treatment. Thus, approximately halfway through this 15-year study, the study has not detected a pattern indicative of a causal association between teriparatide treatment and osteosarcoma in humans. © 2012 American Society for Bone and Mineral Research.
OSTEOSARCOMA; EPIDEMIOLOGY; TERIPARATIDE; SURVEILLANCE; PARATHYROID HORMONE (PTH)
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.
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.
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.
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.
This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs.
BMD; Bone markers; Bone turnover; Osteoporosis; Postmenopausal women; Teriparatide
In this study, a pharmacodynamic model is developed, based on calcium–parathyroid hormone (PTH) homeostasis, which describes the concentration–effect relationship of a negative allosteric modulator of the calcium-sensing receptor (CaR) in rats. Plasma concentrations of drug and PTH were determined from plasma samples obtained via serial jugular vein sampling following single subcutaneous doses of 1, 5, 45, and 150 mg/kg to male Sprague–Dawley rats (n = 5/dose). Drug pharmacokinetics was described by a one-compartment model with first-order absorption and linear elimination. Concentration-time profiles of PTH were characterized using a model in which the compound allosterically modulates Ca+2 binding to the CaR that, in turn, modulates PTH through a precursor-pool indirect response model. Additionally, negative feedback was incorporated to account for tolerance observed at higher dose levels. Model fitting and parameter estimation were conducted using the maximum likelihood algorithm. The proposed model well characterized the data and provided compound specific estimates of the Ki and cooperativity constant (α) of 1.47 ng/mL and 0.406, respectively. In addition, the estimated model parameters for PTH turnover were comparable to that previously reported. The final generalized model is capable of characterizing both PTH–Ca+2 homeostasis and the pharmacokinetics and pharmacodynamics associated with the negative allosteric CaR modulator. As such, the model provides a simple platform for analysis of drugs targeting the PTH–Ca+2 system.
allosteric; bone; calcium sensing receptor; ionized calcium; osteoporosis; parathyroid hormone; pharmacodynamics; pharmacokinetics
Osteoporosis is a condition of impaired bone strength that results in an increased risk of fracture. The current and most popular pharmacological options for the treatment of osteoporosis include antiresorptive therapy, in particular, oral bisphosphonates (alendronate, risedronate, ibandronate). Anabolic agents like teriparatide have widened our therapeutic options. They act by directly stimulating bone formation and improving bone mass quantity and quality. Two forms of recombinant human parathyroid hormone (PTH) are available : full-length PTH (PTH 1–84; approved in the EU only) and the 1–34 N-terminal active fragment of PTH (teriparatide, US FDA approved). This review aims to discuss the benefits of teriparatide beyond the currently licensed indications like fracture healing, dental stability, osteonecrosis of jaw, hypoparathyroidism, and hypocalcemia.
Forsteo; osteoporosis; parathormone; teriparatide
Once-daily injections of teriparatide initially increase biochemical markers of bone formation and resorption, but markers peak after 6–12 months and then decline despite continued treatment. We sought to determine whether increasing teriparatide doses in a stepwise fashion could prolong skeletal responsiveness. We randomized 52 postmenopausal women with low spine and/or hip bone mineral density (BMD) to either a constant or an escalating subcutaneous teriparatide dose (30 mcg daily for 18 months or 20 mcg daily for 6 months, then 30 mcg daily for 6 months, then 40 mcg daily for 6 months). Serum procollagen I N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type I collagen were assessed frequently. BMD of the spine, hip, radius, and total body was measured every 6 months. Acute changes in urinary cyclic AMP in response to teriparatide were examined in a subset of women in the constant dose group. All bone markers differed significantly between the two treatment groups. During the final six months, bone markers declined in the constant dose group but remained stable or increased in the escalating dose group (all markers, p<0.017). Nonetheless, mean area under the curve did not differ between treatments for any bone marker, and BMD increases were equivalent in both treatment groups. Acute renal response to teriparatide, as assessed by urinary cyclic AMP, did not change over 18 months of teriparatide administration. In conclusion, stepwise increases in teriparatide prevented the decline in bone turnover markers that is observed with chronic administration without altering BMD increases. The time-dependent waning of the response to teriparatide appears to be bone-specific.
teriparatide; parathyroid hormone; osteoporosis; bone turnover markers; bone densitometry
Osteoporosis is a chronic condition leading to an increased risk of developing fractures, with high morbidity and mortality in aging population. Efficacy of anti-osteoporotic treatment is based on drug potency but also on compliance and persistence to treatment regimen, which is very low, as already described for other diseases. Teriparatide (TPTD) is the first anabolic agent developed for the treatment of osteoporosis.
Since it appears that persistence to Teriparatide declines over time, aim of this pilot multicenter observational study was to evaluate persistence and adherence to TPTD (20 μg daily injection regimen for 18 months) treatment (PATT) in patients affected by severe osteoporosis in an every day clinical practice.
Patients affected by severe osteoporosis were selected among those who referred to 5 different specialized centers for osteoporosis in North, Center and South of Italy. A sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the Italian osteoporosis guidelines was included. At the beginning of TPTD treatment patients were instructed on the use of the device by the referring specialist of the center, a resident fellow or a nurse. Bone biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18 months. Patients were visited at time 0 and after 6, 12 and 18 months for clinical follow up.
The results included observations of 441/475 patients (98% women) who completed the 18 months treatment; mean age for women was 73±8 and for men 65±9. After 6 months of TPTD treatment persistence was of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of 100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was usually higher within the first 6 months of TPTD treatment. Most common adverse events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%, hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were not reason for stopping treatment.
The persistence and adherence to TPTD treatment obtained in this multicenter observational real life study was very high as compared to studies performed by others. These encouraging results suggest that different key factors such quality of information, frequency of visits, motivations given to patients, opportunity to call the doctor might play a pivotal role in the high persistence and adherence to TPTD treatment obtained in our study and need to be carefully considered before prescribing chronic anti-osteoporotic therapy.
osteoporosis; pharmacological treatment; teriparatide; adherence; persistence
Parathyroid hormone (PTH) changes morphology of osteoclasts within minutes after its systemic administration. The aim of our study was to test in healthy men whether both exogenous and endogenous PTH could change acutely (minutes to hours) the serum cross-linked C-telopeptide of type I collagen (beta CTX), which is released during osteoclastic resorption of bone. Twelve healthy men (age range 24–34 yr) were each studied during 180 min on a control period, after a single subcutaneous injection of teriparatide, and after 30 min EDTA infusion to stimulate endogenous PTH secretion. The tests were started after overnight fast, 3 h after a standard calcium load. The EDTA infusion induced a significant decrease in serum ionized calcium (by 8.5% at 33 min) and a significant increase in plasma PTH (by 305% at 33 min). Both the EDTA and teriparatide resulted in a significant increase in beta CTX (p < 0.001) with maximum increases of 64% and 80%, respectively. A mild, but significant decrease in beta CTX was observed during the control test period. In conclusion, single-dose teriparatide injection as well as a stimulation of endogenous PTH in healthy men results in an acute increase of the bone resorption marker.
bone resorption; calcium; C-telopeptide; parathyroid hormone; teriparatide
We studied the use of teriparatide in postmenopausal women with severe osteoporosis.
Two groups (A and B) of patients affected by severe osteoporosis (T-score ⩽−2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph).
Group A was treated for 18 months with 20 μg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry.
Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%.
Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%.
After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%).
The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B.
The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.
teriparatide; quality of life; severe osteoporosis
The authors describe a unique presentation of celiac disease as multiple non-traumatic fractures in a young male without gastrointestinal complaints. A 29-year-old man presented with back pain and was found to have a non-traumatic compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies. Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no gastrointestinal complaints, but serologic studies were positive to include an elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D supplementation as well as teriparatide. Follow up bone density showed improvement and has no further fractures to date. Primary care physicians, gastroenterologists, and endocrinologists must have a high index of clinical suspicion for celiac disease in any patient who presents with low bone density regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal complaints.
Fracture leads to local and systemic catabolic physiologic changes. As teriparatide is an agent used to treat osteoporosis in patients with fragility fractures, it is unclear whether teriparatide treatment alters bone mineral density (BMD) and bone markers when given to patients with fractures.
We asked whether BMD and bone marker responses would be blunted in patients with fractures placed on teriparatide after fracture compared with patients without fractures on teriparatide.
Patients and Methods
We retrospectively collected data from 141 patients treated with teriparatide for osteoporosis. Seventy-seven patients received teriparatide after fractures (fracture group), whereas 64 were treated for other indications (nonfracture group). We determined BMD at the lumbar spine and at the proximal femur before and 12 and 24 months posttreatment. Bone markers (urine N-telopeptide [urine NTX], bone-specific alkaline phosphatase [BALP]) were measured at baseline and 3, 12, and 24 months posttreatment.
Mean lumbar spine and hip BMDs at last followup increased from baseline with no differences between groups to approximately 9% and 4% at 24 months, respectively. Both bone markers increased from baseline in the nonfracture group, peaking at 12 months. For the fracture group, only urine NTX increased at 3 and 12 months posttreatment. Although the peak levels of both bone markers in the nonfracture group were greater, there was no difference between the two groups.
Fracture does not have a negative effect on the BMD and bone marker responses to teriparatide treatment. Clinicians should anticipate comparable BMD responses when treating patients with teriparatide for osteoporotic fractures and for other indications.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged ≥75 years. Data on clinical fractures, back pain (visual analogue 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. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged ≥75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to <36–month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged ≥75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study.
Age; Back pain; Fracture; Health-related quality of life; Osteoporosis; Teriparatide
Full length (1-84) parathyroid hormone (PTH) was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84) in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD) was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.
PTH (1-84); full-length parathyroid hormone; osteoporosis treatment
An 82-year-old male, a known case of severe osteoporosis with vertebral fracture and prostatic carcinoma, was treated with gonadotropin releasing hormone analogue, calcium carbonate, cholecalciferol sachet and injection teriparatide. His diet consisted of milk and curd. He developed altered behavior and generalized weakness, and on investigation, hypercalcemia, hypokalemia, and metabolic alkalosis with low parathyroid hormone levels were detected. Injection teriparatide was stopped and he was managed with forced saline diuresis and injection zoledronic acid. He was diagnosed as a case of milk alkali syndrome in whom teriparatide and prolonged immobilization played a permissive role in the development of hypercalcemic encephalopathy.
Hypercalcemic encephalopathy; milk alkali syndrome; osteoporosis; teriparatide
A vertebral fracture is a serious symptom of osteoporosis. Vertebral fractures cause moderate-to-severe back pain for a shorter or longer duration, increase the risk of a subsequent vertebral fracture approximately four-fold, reduce quality of life significantly and are associated with increased mortality. In order to choose the optimal treatment for the patient, the severity and type of osteoporosis should be investigated. Prevention of new osteoporotic fractures can be accomplished through treatment with both antiresorptive and anabolic treatments. The antiresorptive treatment modalities comprise calcium, vitamin D, bisphosphonates, hormone therapy, selective oestrogen receptor modulators (SERMs), strontium ranelate, receptor activator of NF-kB ligand (RANKL) antibody and calcitonin. The anabolic treatments comprise teriparatide and parathyroid hormone [(PTH)-(1–84)]. Adherence with treatment of osteoporosis is generally poor and therefore once the choice of treatment has been made and the patient has been instructed properly, long-term adherence to the treatment should be secured through information and regular control visits.
adherence; bisphosphonate; oestrogen; osteoporosis; RANKL antibody; SERM; strontium ranelate; vertebral fracture
Vertebral fractures have been associated with back pain, functional limitations and reduced health-related quality of life (HRQoL). Teriparatide is the first effective anabolic agent that demonstrated to significantly reduce the risk of vertebral fracture by 65%, as compared to placebo.
The aims of this study were to evaluate the effectiveness of teriparatide treatment on back pain-related functional limitations and to investigate on patients HRQoL.
Materials and methods
In this prospective observational pilot study osteoporotic patients, who were prescribed teriparatide therapy and a supplementation of calcium and vitamin D, were asked to answer to two self-administered questionnaires: the Spine Pain Index (SPI) and the SF-12 (at the recruitment, after 6, 12, and 18 months).
Fifty-two women were evaluated (mean age of 70.58 yrs). The mean SPI score passed from 50.01 at baseline to 32.20 at 18 months. The mean SF-12 PCS score passed from 30.00 at baseline to 36.79 at 18 months, while the mean SF-12 MCS score was already within the normality range at baseline, constantly improving during the 18 months.
In conclusion, 18 months of treatment with teriparatide has to be considered an effective therapeutic option for women with severe osteoporosis and vertebral fractures, in a real-life clinical setting, to improve both back pain related disability and quality of life.
osteoporosis; teriparatide; back-pain; functional limitation; health-related quality of life
Raloxifene is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raloxifene decreases the incidence of vertebral fractures by 30%–50% in postmenopausal women with osteoporosis but has not been shown to decrease the incidence of hip fractures or other non-vertebral fractures. At the present time, estrogen-replacement therapy and bisphosphonate treatment are the only medical treatments that are proven to prevent hip fractures with the exception of vitamin D and calcium replacement, which has been shown to prevent hip fractures in elderly individuals and nursing home residents. Raloxifene has been shown to have additive effects on bone turnover and bone mineral density (BMD) when used along with alendronate and teriparatide. Raloxifene could have a role in renal failure as it has been shown to increase BMD of the vertebra over 1 year of therapy. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. The increased incidence of venous thromboembolism is the main concern of raloxifene therapy and previous history of venous thromboembolism is a contraindication for use of raloxifene. Raloxifene has a role in treatment of vertebral osteoporosis in older women. The decision to use raloxifene should be based on evaluation of fracture risk and on potential other benefits than fracture reduction along with consideration of side effects.
SERM; raloxifene; osteoporosis; women; fractures; old age
Glucocorticoids (GC)-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, which leads to an increased fracture risk in patients. The normal bone turnover depends on a balance between osteoblasts and osteoclasts activity and GC can cause a rapid bone loss, decreasing bone formation and increasing bone resorption. The decreased bone formation is mainly due to the GC-induced apoptosis of both osteoblasts and osteocytes, while the increased bone resorption is due to the increased life-span of pre-existing osteoclasts. Bisphosphonates are clearly effective in preventing and treating GIOP but anabolic therapeutic strategies are the new promising therapeutic alternative. Experimental and clinical studies indicate that teriparatide, the active (1–34) parathyroid hormone (PTH) molecule, is efficacious for the treatment of GIOP, being able to induce an increase in bone mass in these patients. Intermittent administration of human PTH (1–34) stimulates bone formation by increasing osteoblast number. Additionally, human PTH (1–34) modulates the level and/or activity of locally produced growth factors and cytokines. Teriparatide has been demonstrated in several clinical studies to significantly decrease the incidence of fractures in patients affected by GIOP. It has recently received an indication for GIOP and its label indication has also been expanded.
glucocorticoids; osteoblasts; osteoclasts; osteoporosis; teriparatide