Treatment Of Severe Osteoporosis Research Articles

EE41 Cost Effectiveness of Romosozumab Followed by Alendronate Versus Teriparatide in the Treatment of Severe Osteoporosis in Greece

EE41 Cost Effectiveness of Romosozumab Followed by Alendronate Versus Teriparatide in the Treatment of Severe Osteoporosis in Greece

Comparison of different parameters between daily and twice-weekly teriparatide in postmenopausal women with severe osteoporosis.

Once-daily teriparatide (D-TPTD) and twice-weekly TPTD (W-TPTD), which are self-administered injections, are generally used in the treatment of severe osteoporosis. This study aimed to reveal the differences in the persistence, safety, and effectiveness of D-TPTD and W-TPTD. A total of 102 patients received D-TPTD (n = 51) and W-TPTD (n = 51). The bone mineral densities (BMD) of the lumbar spine, total hip, and femoral neck were measured using dual energy X-ray absorptiometry. The persistence and effectiveness of the two treatments were compared at 12months. The persistence in the D-TPTD and W-TPTD groups was 80.4% and 66.7% at 12months, respectively (p = 0.178). The % changes (Δ) in BMD values from baseline for the lumbar spine in the D-TPTD were significantly higher than those in the W-TPTD (11.2% vs. 6.3%; p < 0.001) at 12months. The ΔBMD values for the total hip (3.7% vs. 1.3%; p = 0.065) and femoral neck (2.2% vs. 1.6%; p = 0.489) did not differ significantly between the two groups at 12months. The incidence of new morphological vertebral fractures in the D-TPTD and W-TPTD groups was 7.3% and 8.6%, respectively, at 12months (p = 1.000). Lumbar spine BMD (LS-BMD) was significantly increased. Moreover, ΔLS-BMD in the D-TPTD group was higher than that in the W-TPTD group. This study showed that the persistence, ΔTH-BMD, ΔFN-BMD and incidence of vertebral fractures did not differ between the two groups.

Foxf2 represses bone formation via Wnt2b/β-catenin signaling

Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.

Molecular enhancement of fracture healing - Is there a role for Bone Morphogenetic Protein-2, parathyroid hormone, statins, or sclerostin-antibodies?

Enhancement of fracture healing has been a hot topic over the last two decades. This narrative review article is aimed to provide an update on current clinical use and evidence on four clinically available agents in the treatment of fracture healing: bone morphogenetic proteins-2 (BMP-2), parathyroid hormone, statins and sclerostin-antibodies. After first promising results from animal and clinical studies in the early 2000s, BMP-2 was studied mainly in open tibia shaft fractures treated with intramedullary nailing. There are conflicting results from different randomized clinical trials (RCTs) regarding fracture healing time and complications compared to BMP-2 free control treatment in open tibia fractures, as BMP-2 could not show significant differences in patients treated with reamed nails compared to BMP-2 free control treatment with reamed nailing only. Given that fact, its official use was limited in Europe to open tibia shaft fractures treated with unreamed tibial nailing by the European Medical Agency (EMA). Another more recent RCT failed to show equivalence of BMP- 2 together with allograft versus autograft for the treatment of tibia fractures with critical size defects. Recombinant human parathyroid hormone has proven anabolic effects on bone metabolism and is commonly used in treatment of severe osteoporosis. Different animal trials suggested an enhancement effect in fracture healing by PTH. In several clinical trials, PTH seems to have a stimulative effect for lower limb fractures. Statins, commonly used in treatment of dyslipidemia, could also enhance fracture healing in animal trials, especially when they were applied locally at the fracture site. For statins, there is only one RCT that failed to show significant effects for the oral administration of statins in undisplaced distal radius fractures. The role of sclerostin in fracture healing has more and more been understood. Application of sclerostin antibodies has been shown to be beneficial for fracture healing in animal trials. However, no RCTs on the effect of sclerostin antibodies on fracture healing have been performed yet. In conclusion, the "magic bullet" for molecular enhancement of fracture healing has not been identified yet, at least not with its optimal dosage and delivery method.

Teriparatide in the treatment of severe osteoporosis: Results of a case series

Teriparatide in the treatment of severe osteoporosis: Results of a case series

Use of teriparatide in treatment of severe osteoporosis in geriatric practice: a clinical case review

Elderly and senile people are characterized by a high prevalence of osteoporosis, which, in turn, increases the risk of fractures, including the repeated ones. Fractures in osteoporosis are an extremely unfavorable complication of the disease, leading to catastrophic consequences in old age. The prevalence of osteoporotic fractures progressively increases with age. At present, the cumulative frequency of hip fractures in women over 80 is about 30%. The proportion of vertebral fractures in women older than 80 years is up to 40% of all vertebral osteoporotic fractures. Despite the tremendous successes achieved in the diagnosis and treatment of osteoporosis, the disease itself and related fractures remain a serious medical, economic and social problem. Prevention of recurrent fractures in geriatric patients is a system of preventive, rehabilitative and therapeutic measures aimed at reducing the risk of falls, choosing an effective therapy, and reducing the risk of recurring fractures. A serious problem in the treatment of osteoporosis in older people is the inefficiency of the antiresorptive therapy due to an age-related decrease in bone formation. There are frequent cases of a continuing decrease in bone density, the occurrence of repeated fractures during ongoing therapy of osteoporosis. Often the therapy of choice in this case is bone-anabolic therapy with teriparatide, which allows one to achieve good results in the accumulation of bone mineral density. In this article, we will present the clinical case of an elderly patient with severe osteoporosis, in which teriparatide became the drug of choice.

Влияние на бюджет системы здравоохранения применения препарата терипаратид при лечении пациентов с тяжелым остеопорозом в сравнении с антирезорбитивными препарами

Objective: budget impact assessment on the healthcare system use of teriparatide in the treatment of severe osteoporosis in comparison with antiresorptive drugs. Material and methods. Study Design – retrospective literature analysis. Methods of pharmacoeconomic analysis: cost analysis, the “budget impact” analysis, sensitivity analysis. In the study, patients were considered as a target group for prescribing the drug teriparatide or antiresorptive therapy with severe postmenopausal osteoporosis with the presumed development of two compression fractures requiring surgical reconstruction. Results. The use of teriparatide in patients with two low-traumatic vertebral fractures will require a cost 1.4% less than treatment with zoledronic acid and 33.07% less than the treatment with alendronic acid and 13.6% less in comparison with the use of denosumab. At a weighted average frequency of 3 clinically significant fractures per year, the use of teriparatide will require 15.0%, 42.9% and 24.7% less cost, respectively. For a group of 1000 patients with 2 fractures per year, the savings over 4 years will amount to 13.7 million rubles, 483.0 million rubles, respectively and 154.1 million rubles. With a more severe course, expressed in an increase in the number of fractures to 3 per year, budget savings over 4 years per 1000 patients will amount to 219.0 million rubles, 930.9 million rubles and 406.0 million rubles, respectively. A sensitivity analysis showed that on a 4-year horizon, the use of teriparatide remains economically feasible with a decrease in the frequency of fractures to 1.95 per year compared to zoledronic acid, to 1.4 per year compared to denosumab and to 0.95 per year compared alendronic acid. Conclusion. Teriparatide is more cost effective than antiresorptive drugs for severe osteoporosis, when an average of 2 clinically significant vertebral fractures per year can be expected in untreated patients requiring surgical reconstruction. In this way, the appointment of teriparatide as the first line of therapy for osteoporosis in patients at high risk of fractures, having more than one clinically significant fracture of the vertebral body in a history is justified from a pharmacoeconomic point of view.

THE PLACE OF STRONTIUM RANELATE IN THE TREATMENT OF PATIENTS WITH OSTEOPOROSIS (RESULTS OF THE MARC PROGRAM)

Strontium ranelate (SR) that has a proven efficacy in reducing the risk of fractures and in increasing bone mineral density is currently recommended as a second choice drug for the treatment of severe osteoporosis (OP) in postmenopausal women and elderly men. Subjects and methods. In 2014–2015, a survey within the framework of the MARC program (The Use of Antiosteoporotic Drugs in Real Clinical Practice) was conducted in 1799 OP patients aged 25 to 92 years, who had been treated for this disease for at least one year. Among the respondents, there were 1696 people aged 50 years and older (mean age, 64±7 years; disease duration, 2.7±2.4 years) (86% women and 14% men) who were the subjects of this survey. Adherence to performed antiosteoporotic therapy was evaluated within the last 12 months before the survey by the following parameters: which drug had been taken; the number of packages used, treatment gaps and compliance with the treatment regimen. Results and discussion. The survey of the patients included in the study showed that 19% of them had received SR at any time over the course of the disease, and 8% had taken the drug within the year preceding the survey. Thus, SR remains a popular drug in real clinical practice for the treatment of severe OP in patients with no history of coronary heart disease, uncontrolled hypertension, cerebrovascular diseases, peripheral artery disease, and a predisposition to thrombosis and thromboembolism.

PMS19 - Cost Benefit Analysis in The Treatment of Severe Osteoporosis from The Public Healthcare System Perspective in Mexico

PMS19 - Cost Benefit Analysis in The Treatment of Severe Osteoporosis from The Public Healthcare System Perspective in Mexico

Perception of severe osteoporosis amongst medical doctors in South Korea: Awareness, impact, and treatment

ObjectivesLittle is currently known about the issues surrounding management and treatment of severe osteoporosis in South Korea. Our objective was to assess doctors' views on the perception, diagnosis, and treatment of severe osteoporosis. MethodsFace-to-face interviews were conducted (16 February–13 March 2015) with 100 doctors (specialists in orthopedic surgery, endocrinology, neurosurgery, family medicine, or rheumatology) who treated ≥5 severe osteoporosis (T-score ≤ −2.5, plus fracture) patients per month. Respondent demographic characteristics, their perception of severe osteoporosis, its impact and treatment, and their views on current practice and unmet needs were assessed. ResultsOf 416 doctors approached, 100 completed the survey (24% response rate). Most doctors (90%) specialized in orthopedic surgery, endocrinology, or neurosurgery. When diagnosing severe osteoporosis, most doctors (79%) considered both bone mineral density and fracture. Almost all doctors (≥91%) ranked disease impact and seriousness highly, but much fewer (≤25%) doctors thought society agreed. Most doctors (89%) had concerns with current treatments, switching treatments because of the efficacy and safety of bisphosphonates (>89%), the efficacy of selective estrogen receptor modulators (>71%), and the high cost of parathyroid hormone (>73%). Parathyroid hormone was ranked highest for efficacy and was preferentially prescribed to severe osteoporosis patients (mean 32.2% of prescriptions) compared with osteoporosis patients overall (3.7%). “Limitations with reimbursement” was the most commonly cited (76%) unmet need. ConclusionsThere are concerns with the safety, efficacy, and affordability of current treatments for severe osteoporosis in South Korea, as well as a perceived lack of disease awareness amongst patients and doctors.

Bisphosphonate-associated osteonecrosis of the jaw

Bisphosphonates (BP) are used in the treatment of severe osteoporosis and metastasis of malignant diseases. A possible relationship between the occurrence of osteonecrosis of the jaw and BP therapy was first described in 2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is difficult to treat. In some cases the condition of the patients is so compromised that only minimally invasive surgery is possible. Histopathologically, osteonecrosis shows the features of chronic sequestered osteomyelitis, which can be found in different areas of the upper and lower jaw. Sometimes extensive resections of the jaw are necessary. Thus, BRONJ can cause mutilation, impairment of function and esthetics in the orofacial system and, thereby, compromise the life quality of the patients. Triggering factors are often tooth extraction without surgical plastic wound closure of the alveoli, but can also be associated with bruises from denture or other minor wounds. The purpose of this article is to present results from our own patient collective, including therapy regime, success rate, and therapy recommendations. The patient populations at three German hospitals were analyzed using a standard questionnaire. The patients in the study group, entered into a follow-up system for early detection of possible BRONJ, were evaluated for treatement outcome. The success rate for prophylactic surgery in asymptomatic patients was very high at 96 %. In the group with symptomatic BRONJ, the outcome was significantly lower (76.4 %). Because of the complex symptoms, close cooperation between oncologists, dentists, and maxillofacial surgeons is required in the treatment of BRONJ. Before starting therapy with bisphosphonates and during the therapy, dental treatment and monitoring of the patient' oral health is necessary.

Bone anabolics in osteoporosis: Actuality and perspectives.

Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation. Antiresorptive drugs decrease the activation frequency, thereby determining a secondary decrease in bone formation rate and a low bone turnover. Bisphosphonates are today's mainstay among antiresorptive treatment of osteoporosis. Also, oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover. Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis. Recombinant-human parathyroid hormone (PTH) has showed to increase bone formation and significantly decrease vertebral fractures in severe patients, but with a modest effect on nonvertebral fractures. The study of Wnt signaling pathway, that induces prevalently an osteoblastic activity, opens large possibilities to antagonists of Wnt-inhibitors, such as sclerostin antibodies and dickkopf-1 antagonists, with potential effects not only on trabecular bone but also on cortical bone.

The Russian Council of Experts for Use of the Innovative Anabolic Agent Forsteo®(Teriparatide) in the Treatment of Severe Osteoporosis

The meeting of the Russian Council of Experts for the use of the novel anabolic agent Forsteo®(teriparatide) to treat osteoporosis (OP) was held in Moscow on June 29, 2013. The meeting was attended by leading Russian OP specialists, including the members of the Russian Osteoporosis Association and its Presidium. The participants of the Council of Experts noted the great social importance of severe OP, which was associated primarily with its consequences, such as fractures causing an increase in disability and mortality rates in elderly people, and discussed the possibilities and benefits of the new approach to treating OP with teriparatide, the first drug permitting the formation of new bone tissue. The experts have recommended teriparatide for use within the registered indications in the following groups of patients: those who have severe OP (≥1 vertebral fractures, hip fracture of vertebral bodies or a fracture of the proximal femur, multiple recurrent fractures of skeletal bones) as first-line therapy; those who had ineffective previous antiosteoporotic therapy (new fractures occurring during the treatment and/or a continuing decline in bone mineral density), those who are intolerant to other medications for OP, or who have contraindications to their use.

Intermittent pamidronate therapy for treatment of severe osteoporosis in postmenopausal women

Intermittent pamidronate therapy for treatment of severe osteoporosis in postmenopausal women

Effect of Intermittent Versus Continuous Parathyroid Hormone in the Cardiovascular System of Rats

Objective:PTH increases ionic calcium concentration in the serum, acting primarily on bone and kidney cells through the type 1 PTH receptor. Interestingly, PTH stimulates bone formation when administrated intermittently but causes severe bone loss with continuous administration. Daily injections of PTH are used as the most promising anabolic agent in the treatment of severe osteoporosis. Elevated PTH is reported an independent risk factor for left ventricle hypertrophy.Design:in rats we investigated the effect of intermittent and continuous administration of PTH on blood pressure, heart rate and development of cardiac hypertrophy and fibrosis.Results:We did not find PTH to induce heart hypertrophy. In contrast, continuous administration of PTH the mRNA level of a hypertrophic marker gene, atrial natriuretic peptide. When comparing the effect of continuously versus injected PTH collagen 1 mRNA was significantly higher in continuously treated animals.Conclusion:our data demonstrated a decrease in heart rate upon continuous administration of PTH in rats. No changes in blood pressure were observed. Moreover, neither intermittent nor continuous administration of PTH induced ventricular hypertrophy. But continuous PTH induced a marker of collagen 1. Thus, these data did not reveal any negative effects of the injection of PTH on the cardiovascular system.

Effect of intravenous pamidronate for treatment of severe osteoporosis in postmenopausal women

Effect of intravenous pamidronate for treatment of severe osteoporosis in postmenopausal women

La hormona paratiroidea en el tratamiento de la osteoporosis

Current treatments available for osteoporosis until recently were active by inhibiting osteoclast activity and, thus, reducing bone remodelling. Intact PTH (PTH 1-84) and its analog, teriparatida (human recombinant PTH 1-34), are a new class of anabolic treatment of osteoporosis. It has been described a positive effect on bone microarchitecture and a reduction of the risk of new fractures due to a bone-forming mechanism.PTH must be considered as an useful alternative in the treatment of severe osteoporosis, both in men and women, in patients with several osteoporosis-related fractures or with a very low bone mineral density (T-score below -3.5) an a high risk for fracture. Other potential uses are glucocorticoid-induced and other secondary osteoporosis. The use of PTH is not recommended for more than 18 months for teriparatida and 24 months for PTH 1-84.

Treatment of severe osteoporosis with alendronate in a patient with lysinuric protein intolerance

Lysinuric protein intolerance is an inborn error of cationic amino acid transport of which osteoporosis is a major feature. Treatment with oral bisphosphonates improves bone mineral density even in severe osteoporosis.

Teriparatide (Biosynthetic Human Parathyroid Hormone 1–34): A New Paradigm in the Treatment of Osteoporosis

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.

MANAGEMENT OF PRIMARY OSTEOPOROSIS

Although there is a great need for better therapeutic approaches to the patient who presents with a fracture, osteoporotic fractures will remain a condition that is more amenable to prevention than treatment. Hormone replacement therapy (HRT) is still considered by many the mainstay for the prevention and the treatment of posrmenopausal osteoporosis. However, there are several controversies regarding HRT, especially the duration of treatment and the risks/benefits ratio. Recent studies have challenged the assumption that HRT conveys real long-term beneficial effects. Raloxifene or other“selective estrogen receptor modulators” (SERMs) should progressively replace HRT in elderly women. Bisphosphonates have demonstrated a clearcut efficacy in the treatment of osteoporosis. Alendronate and risedronate have been the most extensively studied bisphosphonates under randomized controlled trials conditions. Both agents can reduce the risk of vertebral and hip fractures by one-fourth to one-half. However, oral bisphosphonates are not without gastro-intestinal toxicity and strict adherence to constraining therapeutic schemes is mandatory. Intermittent treatments are alredy in use. Weekly alendronate is as efficient as daily therapy and improves treatment compliance. Newer more potent bisphosphonates, such as oral ibandronate or intravenous zoledronic acid, will allow much less frequent administration. The anti-fracture efficacy of yearly zoledronic acid infusions is thus currently tested. On the other hand, bone-forming agents, such as daily subcutaneous injections of teriparatide (rhPTH 1-34) offer exciting perspectives for the treatment of severe osteoporosis despite the complexity of such therapy.Osteoporosis is now defined as a disease characterized by a low bone mass and a microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Osteoporosis is a major public health problem and the current risk for a 50-yr old white woman to suffer from a hip, a vertebra or a wrist fracture is around 40%, 17.5% of which will be hip fractures. The incidence of fractures is about three times lower in men than in women but the mortality due to hip fractures is higher in men. The cost of osteoporotic fractures is considerable and is estimated in USA to be more than 20 x 109 $ per year (1). The different patterns of bone loss are the result of distinct cellular mechanisms and it is probably an oversimplification to consider primary osteoporosis as a single disease (2). The inexorable age-related bone loss seen in both sexes is the result of gradual thinning of trabeculae brought about by declining osteoblast function. Thus the osteoblast teams become less and less capable of refilling the resorption cavities created by the osteoclasts, so the thickness of the trabecular packets, and consequently the trabeculae themselves, declines. By contrast, the rapid postmenopausal bone loss is viewed as osteoclast- mediated. As estrogens concentrations fall, the osteoclasts become hyperactive, penetrate too deeply into the trabecular plates, and perforate them. Once the trabecular plate is perforated, the template for new bone formation is lost, formation and resorption are uncoupled, i.e. do not occur at the same remodeling site, and tissue is rapidly lost. The trabeculae become more widely separated and intertrabecular connectivity is reduced. As if that were not enough, the postmenopausal increase in activation frequency of remodelling units adds to the deleterious effects of the hyperactive osteoclasts. The rapid disruption of trabecular microarchitecture that occurs after menopause has more deleterious consequences for bone strength that does simple trabecular thinning. This fact accounts for the sharp rise in crush fractures of the vertebrae, which are rich in cancellous bone, among postmenopausal women. In contrast, the incidence of fractures characteristic of“age-related” osteoporosis, such as hip fracture, increases exponentially after 65 years.Bone mineral density (BMD) as measured by dualenergy X-ray absorptiometry (DXA) is the most common method for the diagnosis of osteoporosis and the threshold of a T-score (number of SD below the «peak bone mass») less than –2.5 is now classically used to establish the diagnosis. The ability of DEXA to predict fracture risk in an untreated population is well-characterized (3). However, changes in BMD following therapeutic intervention do not appear to predict fracture reduction as well as BMD predicts fracture risk prior to treatment (4). There is a growing interest in biochemical markers of bone turnover for that matter.This article will briefly review the recent therapeutic developments and the perspectives for the prevention and treatment of primary osteoporosis. For more complete assessments, the reader is referred to recent reviews (5).