A Phase I Randomized Trial of Once-Daily Versus Twice-Daily Recombinant Human Parathyroid Hormone (1-84) for Hypoparathyroidism.

Recombinant human parathyroid hormone (1-84), rhPTH(1-84), is an approved adjunctive treatment to oral calcium and active vitamin D for adult patients with hypoparathyroidism; however, there is limited information on the effect of twice daily (BID) dosing of rhPTH(1-84). This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism. The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 µg BID, 50 µg BID, and 100 µg once daily (QD) with or without supplemental oral calcium. Safety and tolerability were evaluated as secondary objectives. In total, 33 patients with chronic hypoparathyroidism completed the study. Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion. The decrease in urinary calcium excretion was numerically greater for BID than QD. Generally, baseline-adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1-84) dose, although this effect was not dose proportional. No new safety findings were observed. Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1-84) dosing. Future long-term studies are warranted to further elucidate the effects of alternative dosing strategies. © 2023 Takeda Development Center Americas, Inc and The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism. OBJECTIVE: This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism. METHODS: This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day). RESULTS: By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 µg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events. CONCLUSION: TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.

Changes in treatment needs of hypoparathyroidism during pregnancy and lactation: A case series.

OBJECTIVE: As only sparse data are available, we aimed to investigate whether needs for activated vitamin D and calcium supplements change in women with hypoparathyroidism during pregnancy and lactation and risk of pregnancy-related complications. DESIGN: Retrospective review of medical records. PATIENTS: Twelve Danish and Canadian patients with chronic hypoparathyroidism who completed 17 pregnancies. MEASUREMENTS: Data were extracted on plasma levels of ionized calcium (P-Ca2+ ) and doses of active vitamin D and calcium supplements during pregnancy (N = 14) and breastfeeding (N = 10). Data on pregnancy complications were available from all 17 pregnancies. RESULTS: Although average doses of active vitamin D (P = .91) and calcium supplements (P = .43) did not change during pregnancies, a more than 20% increase or decrease in dose of active vitamin D was needed in more than half of the pregnancies in order to maintain normocalcemia. Five women (36%) developed hypercalcaemia by the end of pregnancy or start of lactation. Median levels of P-Ca2+ increased from 1.20 mmol/L in third trimester to 1.32 mmol/L in the post-partum period (P < .03). Accordingly, the average dose of active vitamin D was significantly reduced (P = .01) during lactation compared to 3rd trimester. One woman developed severe pre-eclampsia (6%). Further four pregnancies (24%) were complicated by polyhydramnios, dystocia and/or perinatal hypoxia. Ten pregnancies required caesarean delivery (59%) with four (24%) being performed as an emergency. CONCLUSION: In chronic hypoparathyroidism, close medical monitoring of the mother with frequent adjustments in the dose of calcium and active vitamin D is required during pregnancy and lactation in order to maintain normocalcemia. Patients should be offered close obstetric care to handle potential perinatal complications. We recommend evaluating the neonate immediately after birth and notifying the paediatrician of the risks of hypocalcaemia as well as hypercalcaemia in the neonate.

MANAGEMENT OF ENDOCRINE DISEASE: Hypoparathyroidism in pregnancy: review and evidence-based recommendations for management.

Purpose Review calcium homeostasis in pregnancy and provide evidence-based best practice recommendations for the management of hypoparathyroidism in pregnancy. Methods We searched MEDLINE, EMBASE and Cochrane databases from January 2000 to April 1, 2018. A total of 65 articles were included in the final review. Conclusions During pregnancy, calcitriol levels increase by two- to-three-fold resulting in enhanced intestinal calcium absorption. The renal filtered calcium load increases leading to hypercalciuria. PTHrP production by the placenta and breasts increases by three-fold, and this may lower the doses of calcium and calcitriol required during pregnancy in mothers with hypoparathyroidism. The literature however describes a wide variation in the required doses of calcium and calcitriol during pregnancy in hypoparathyroid mothers, with some women requiring higher doses of calcitriol, whereas others require lower doses. Close monitoring is necessary as hypercalcemia in the mother may suppress the fetal parathyroid gland development. Also hypocalcemia in the mother is harmful as it may result in secondary hyperparathyroidism in the fetus. This may be associated with demineralization of the fetal skeleton and the development of intrauterine fractures. Inadequate treatment of hypoparathyroidism may also result in uterine contractions and an increased risk of miscarriage. Treatment targets during pregnancy are to maintain a low normal serum calcium. Calcium, calcitriol and vitamin D supplements are safe during pregnancy. Close monitoring of the mother with a multidisciplinary team is advised for optimal care. If calcium homeostasis is well controlled during pregnancy, most women with hypoparathyroidism have an uncomplicated pregnancy and give birth to healthy babies.

Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus.

PURPOSE: To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults. METHODS: Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords 'hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy'. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism. RESULTS: Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults. MAIN CONCLUSIONS: Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.

A weekly 35,000 IU vitamin D supplementation improves bone turnover markers in vitamin D deficient Saudi adolescent females.

This study examined the effects of weekly 35,000 IU vitamin D supplementation for 4 weeks on bone turnover markers (BTMs). There was improvement in the levels of parathyroid hormone (PTH), osteocalcin, and carboxy-terminal telopeptides of crosslinks of type 1 collagen (ßCTX) which paralleled the increase in vitamin D levels. PURPOSE: The effects of vitamin D supplementation on bone turnover markers (BTMs) have been inconsistent. This study examined the effects of weekly 35,000 IU vitamin D supplementation for 1 month on BTMs. METHODS: Sixty-eight vitamin D deficient adolescent females were given 35,000 IU of vitamin D3 for 4 weeks. Pre and post intervention blood samples were taken for 25(OH) D, PTH, osteocalcin and ßCTX. RESULTS: There was a significant increase in serum 25 (OH) D in the post intervention period which was accompanied by a significant decrease in PTH, osteocalcin and ßCTX (P < 0.001). CONCLUSIONS: We concluded that weekly 35,000 IU vitamin D supplementation for 4 weeks results in significant improvement of BTMs.

Ostéoporose pendant la ménopause.

OBJECTIF: Offrir aux fournisseurs de soins de santé des lignes directrices quant à la prévention, au diagnostic et à la prise en charge clinique de l'ostéoporose postménopausique. ISSUES: Stratégies visant à identifier et à évaluer les femmes exposées à des risques élevés; utilisation de la densité minérale osseuse et des marqueurs du renouvellement des cellules osseuses pour l'évaluation du diagnostic et de la réaction à la prise en charge; et recommandations quant à la nutrition, à l'activité physique et au choix du traitement pharmacologique en vue de prévenir l'ostéoporose et d'en assurer la prise en charge. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE et The Cochrane Library le 30 août et le 18 septembre 2012, respectivement, au moyen d'un vocabulaire contrôlé (p. ex. « osteoporosis ¼, « bone density ¼, « menopause ¼) et de mots clés (p. ex. « bone health ¼, « bone loss ¼, « BMD ¼) appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles publiés en anglais ou en français. Les résultats ont été restreints aux documents publiés à partir de 2009. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en mars 2013. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. VALEURS: La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). COMMANDITAIRE: La Société des obstétriciens et gynécologues du Canada. RECOMMANDATIONS.

Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or nonsuppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium level and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy. DESIGN: Phase 3, double-blind, multi centere, randomized, placebo-controlled study. METHODS: Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for ≤28 weeks. MAIN OUTCOME MEASURE: Achievement of a normal mean corrected total serum calcium concentration of ≤10.3 mg/dl (2.575 mmol/l). RESULTS: Baseline median (quartile 1 (Q1), Q3) serum PTH was 164.0 (131.0, 211.0) pg/ml and mean (s.d.) serum Ca was 11.77 (0.46) mg/dl. Serum Ca normalized (≤10.3 mg/dl) in 75.8% of cinacalcet- vs 0% of placebo-treated subjects (P<0.001). Corrected serum Ca decreased by ≥1.0 mg/dl from baseline in 84.8% of cinacalcet- vs 5.9% of placebo-treated subjects (P<0.001). Least squares mean (s.e.m.) plasma PTH change from baseline was -23.80% (4.18%) (cinacalcet) vs -1.01% (4.05%) (placebo) (P<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (AEs) (27 vs 20) and serious AEs (three vs four). Most commonly reported AEs were nausea and muscle spasms. CONCLUSIONS: These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.

Medical management of primary hyperparathyroidism: proceedings of the fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism.

OBJECTIVE: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The only available definitive therapy is parathyroidectomy, which is appropriate to consider in all patients. The purpose of this report is to provide an update on calcium and vitamin D supplementation and medical management for those patients with PHPT who cannot or do not want to undergo surgery. METHODS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search was undertaken, and relevant articles published between 2008 and 2013 were reviewed in detail. The questions were addressed by the panel of experts, and consensus was established at the time of the workshop. CONCLUSIONS: The recommended calcium intake in patients with PHPT should follow guidelines established for all individuals. It is not recommended to limit calcium intake in patients with PHPT who do not undergo surgery. Patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to ≥ 50 nmol/L (20 ng/mL) at a minimum, but a goal of ≥75 nmol/L (30 ng/mL) also is reasonable. Pharmacological approaches are available and should be reserved for those patients in whom it is desirable to lower the serum calcium, increase BMD, or both. For the control of hypercalcemia, cinacalcet is the treatment of choice. Cinacalcet reduces serum calcium concentrations to normal in many cases, but has only a modest effect on serum PTH levels. However, bone mineral density (BMD) does not change. To improve BMD, bisphosphonate therapy is recommended. The best evidence is for the use of alendronate, which improves BMD at the lumbar spine without altering the serum calcium concentration. To reduce the serum calcium and improve BMD, combination therapy with both agents is reasonable, but strong evidence for the efficacy of that approach is lacking.

Evaluation and management of skeletal health in celiac disease: position statement.

OBJECTIVE: To review the evaluation and management of skeletal health in patients with celiac disease (CD), and to make recommendations on screening, diagnosis, treatment and follow-up of low bone mineral density (BMD) in CD patients. METHODS: A multidisciplinary team developed clinically relevant questions for review. An electronic search of the literature was conducted using the MEDLINE and EMBASE databases from 1996 to 2010. All original studies, reviews and guidelines, both pediatric and adult, were included. A document summarizing the results of the review and proposed recommendations was prepared and underwent multiple revisions until consensus was reached. RESULTS: At diagnosis, approximately one-third of adult CD patients have osteoporosis, one-third have osteopenia and one-third have normal BMD. Children with CD have low bone mass at diagnosis. Adult and pediatric CD patients are at increased risk of fractures. DISCUSSION: For adults, serum calcium, albumin, 25(OH) vitamin D3, parathyroid hormone and 24 h urine calcium testing should be performed at diagnosis; patients with 'classic' CD and those at risk for osteoporosis should undergo a dual x-ray absorptiometry scan. An abnormal baseline dual x-ray absorptiometry scan should be repeated one to two years after initiation of a gluten-free diet (GFD). For children, BMD should be assessed one year after diagnosis if GFD adherence is not strict. A GFD is the most important treatment for bone loss. Supplemental antiresorptives may be justified in those who remain at high fracture risk (eg, postmenopausal women, older men) after implementation of a GFD. CONCLUSION: Current evidence does not support the screening of all CD patients for low BMD at diagnosis. Follow-up BMD assessment should be performed one to two years after initiation of a GFD.

Hypoparathyroidism.

Hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia and low or inappropriately normal levels of parathyroid hormone (PTH). Pseudohypoparathyroidism is characterized by similar findings however PTH is elevated due to PTH resistance. PTH is a key calcium regulating hormone essential for calcium homeostasis, vitamin D-dependant calcium absorption, renal calcium reabsorption and renal phosphate clearance. The most common cause of hypoparathyroidism is iatrogenic in the setting of anterior neck surgery. Hypoparathyroidism may be due to congenital or acquired disorders. Causes include autoimmune diseases, genetic abnormalities, destruction or infiltrative disorders of the parathyroids. Impaired secretion of PTH may be seen with hypomagnesemia or hypermagnesemia Work-up includes a comprehensive history, physical examination, and a relevant biochemical investigation. Treatment of symptomatic or profound asymptomatic hypocalcemia (Corrected Calcium (Ca) < 1.9 mmol/L) is aimed at rapid intravenous administration of calcium and oral supplementation of vitamin D metabolites. Oral calcium and vitamin D analogs are critical in the treatment of hypocalcemia. In the long-term management of hypoparathyroidism thiazide diuretics are of value as they enhance renal calcium reabsorption and increase serum calcium and are of particular benefit in those with activating mutations of the calcium-sensing receptor. Parathyroid hormone replacement is of great value in improving serum calcium and lowering serum phosphate as well as the doses of calcium and calcitriol supplementation required. It has been shown to lower urinary calcium losses. Careful monitoring of vitamin D, phosphorous, and calcium is necessary during acute and long-term therapy. Although hypocalcemic patients commonly present with symptoms of neuromuscular irritability with perioral numbers paresthesias, tingling, seizures and, bronchospasm; hypocalcemia may be identified on the biochemical profile of an asymptomatic patient.

Hypocalcemia: updates in diagnosis and management for primary care.

OBJECTIVE: To provide family physicians with an evidence-based approach to the diagnosis and management of hypocalcemia. Quality of evidence MEDLINE and EMBASE articles from 2000 to 2010 were searched, with a focus on the diagnosis and management of hypocalcemia. Levels of evidence (I to III) were cited where appropriate, with most studies providing level II or III evidence. References of pertinent papers were also searched for relevant articles. Main message Chronic hypocalcemia is commonly due to inadequate levels of parathyroid hormone or vitamin D, or due to resistance to these hormones. Treatment focuses on oral calcium and vitamin D supplements, as well as magnesium if deficiency is present. Treatment can be further intensified with thiazide diuretics, phosphate binders, and a low-salt and low-phosphorus diet when treating hypocalcemia secondary to hypoparathyroidism. Acute and life-threatening calcium deficit requires treatment with intravenous calcium.The current treatment recommendations are largely based on expert clinical opinion and published case reports,as adequately controlled clinical trial data are not currently available. Complications of current therapies for hypoparathyroidism include hypercalciuria, nephrocalcinosis, renal impairment, and soft tissue calcification. Current therapy is limited by serum calcium fluctuations. Although these complications are well recognized, the effects of therapy on overall well-being, mood, cognition, and quality of life, as well as the risk of complications,have not been adequately studied. CONCLUSION: Family physicians play a crucial role in educating patients about the long-term management and complications of hypocalcemia. Currently, management is suboptimal and marked by fluctuations in serum calcium and a lack of approved parathyroid hormone replacement therapy for hypoparathyroidism.

Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) in association with use of bisphosphonate (BP) has been described primarily in cancer patients receiving high-dose intravenous BP. The frequency of the condition in patients with osteoporosis appears to be low. We evaluated the frequency of BP-associated ONJ in Ontario in the cancer population and in those receiving BP for osteoporosis and metabolic bone disease. METHODS: A survey developed by representatives of the Ontario Society of Oral and Maxillofacial Surgeons was mailed to Ontario oral and maxillofacial surgeons (OMFS) in December 2006, asking oral surgeons to provide information on cases of ONJ seen in the previous 3 calendar years (2004 to 2006). OMFS were subsequently contacted by telephone if they had not responded or if they had reported cases of ONJ. The frequency of ONJ in association with BP use was estimated from the number of patients with filled prescriptions for BP in Ontario between 2004 and 2006. The cumulative incidence of ONJ was calculated separately for patients using intravenous (IV) BP for cancer treatment and for patients using oral or IV BP for osteoporosis or other metabolic bone disease. RESULTS: Between 2004 and 2006, 32 ONJ cases were identified. Nineteen patients received IV BP for cancer treatment and 13 patients received oral or IV BP for osteoporosis or metabolic bone disease. Over a 3-year period the cumulative incidence of BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or other metabolic bone disease observations (1.04 per 100,000). The relative risk of low dose IV/oral BP-associated ONJ was 0.002 (95% CI 0.001, 0.005) compared to high-dose IV BP. Other risk factors for ONJ were present in all cases in whom detailed assessment was available. The median duration of exposure to BP was 42 months (range 36 to 120 mo) and 42 months (range 11 to 79 mo) in osteoporosis patients and cancer patients, respectively. CONCLUSION: Over a 3-year period, the cumulative incidence for BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or metabolic bone disease observations (1.04 per 100,000). This study provides an approximate frequency of BP-associated ONJ in Canada. These data need to be quantified prospectively with accurate assessment of coexisting risk factors.

Management of osteoporosis in men: an update and case example.

In 2002, Osteoporosis Canada published clinical practice guidelines for the diagnosis and management of osteoporosis. The current paper supplements that guideline and provides a review and synthesis of the current literature on the diagnosis and management of osteoporosis in men.

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.

PURPOSE: To evaluate serum 25-hydroxyvitamin D [25(OH)D] concentrations and factors related to vitamin D inadequacy in postmenopausal North American women receiving therapy to treat or prevent osteoporosis. METHODS: Serum 25(OH)D and PTH were obtained in 1536 community-dwelling women between November 2003 and March 2004. Multivariate logistic regression was used to assess risk factors for suboptimal (<30 ng/ml) 25(OH)D. RESULTS: Ninety-two percent of study subjects were Caucasian, with a mean age of 71 yr. Thirty-five percent resided at or above latitude 42 degrees north, and 24% resided less than 35 degrees north. Mean (sd) serum 25(OH)D was 30.4 (13.2) ng/ml: serum 25(OH)D was less than 20 ng/ml in 18%; less than 25 ng/ml in 36%; and less than 30 ng/ml in 52%. Prevalence of suboptimal 25(OH)D was significantly higher in subjects who took less than 400 vs. 400 IU/d or more vitamin D. There was a significant negative correlation between serum PTH concentrations and 25(OH)D. Risk factors related to vitamin D inadequacy included age, race, body mass index, medications known to affect vitamin D metabolism, vitamin D supplementation, exercise, education, and physician counseling regarding vitamin D. CONCLUSIONS: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.

Advances in osteoporosis therapy. 2003 update of practical guidelines.

OBJECTIVE: To review evidence for current therapies for postmenopausal osteoporosis and to establish practical guidelines for management of osteoporosis by family physicians. QUALITY OF EVIDENCE: MEDLINE was searched from January 1990 to January 2003. Articles retrieved were graded by level of evidence (I to III). Recommendations for diagnosis and therapy were based on evidence from randomized controlled trials and meta-analyses. MAIN MESSAGE: Osteoporosis is treatable. Early diagnosis and intervention is recommended. After excluding secondary causes of osteoporosis, physicians should advise patients to take appropriate calcium and vitamin D supplementation. Those with osteopenia at risk of fractures and those with established osteoporosis need additional therapy. CONCLUSION: Approved pharmacologic therapies include alendronate, risedronate, raloxifene, calcitonin, cyclical etidronate, and hormone replacement therapy. Family physicians can help with early diagnosis and intervention and should discuss lifestyle modification with patients.