ABSTRACT
Context: Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited. Case Descriptions: We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: -130 ± 222â mg/24â hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction. Conclusion: In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.
ABSTRACT
Summary: We present the first report of use of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) in a hypoparathyroid patient during early pregnancy and lactation. The patient developed postoperative hypoparathyroidism as a 28-year-old woman following total thyroidectomy for multinodular goiter. She was not well controlled with conventional therapy, and started rhPTH(1-84) in 2015 following its approval in the United States. She became pregnant in 2018 at age 40. She discontinued rhPTH(1-84) therapy at 5 weeks gestation but resumed in the postpartum period while breastfeeding. Her daughter's serum calcium was borderline elevated at 8 days postpartum but within the normal range at 8 weeks postpartum. The patient stopped nursing at around 6 months postpartum. Her daughter is now at 4 years and 5 months of age and is healthy and meeting developmental milestones. She was again pregnant at 8 months postpartum from her first pregnancy, and she made an informed decision to continue parathyroid hormone. At 15 weeks gestation, rhPTH(1-84) was recalled in the United States due to issues with the delivery device, and she discontinued rhPTH(1-84) treatment and resumed calcium and calcitriol supplements. She gave birth to a baby boy at 39 weeks in January 2020. At 3 years and 2 months of age, he is overall healthy. Further data are needed regarding the safety of rhPTH(1-84) in pregnancy and lactation. Learning points: rhPTH(1-84) is approved for therapy of patients with hypoparathyroidism; however, there are no data regarding the safety of treatment during nursing and pregnancy. There are multiple alterations in mineral metabolism during normal pregnancy and lactation.
ABSTRACT
Hypoparathyroidism (HypoPT) is a disorder characterized by hypocalcemia, low or absent parathyroid hormone (PTH) levels, reduced bone remodeling, and high areal bone mineral density (aBMD). PTH is a therapeutic option, yet data on the prolonged clinical and skeletal effects of PTH treatment are limited. We tracked annual daily doses of calcium and active vitamin D supplements, calciotropic biochemistries, estimated glomerular filtration rate (eGFR), and aBMD measurements in 27 HypoPT patients (16 postsurgical, 11 nonsurgical) who were treated with recombinant human PTH(1-84) [rhPTH(1-84)] for at least 8 (n = 27) and up to 12 (n = 14) years. We also performed high-resolution-peripheral quantitative computed tomography (HRpQCT) imaging and report results at baseline, 5, 8, and 12 years of rhPTH(1-84) treatment. With prolonged use of rhPTH, reductions in the need for supplemental calcium and active vitamin D were maintained. The eGFR did not decline. Serum calcium was maintained within the lower limit of the normal range. aBMD by dual-energy X-ray absorptiometry (DXA) showed an increase at the lumbar spine and a decrease at the distal 1/3 radius. By HRpQCT, cortical volumetric BMD (vBMD) at the tibia decreased at year 5: -20.0% ± 1.5%. The magnitude of this reduction was mitigated in year 8: -8.5% ± 1.6% and in year 12: -10.3% ± 2.2% but all were significantly below the mean baseline value (p < 0.001). A similar pattern of decline was observed at the radius. Cortical porosity progressively increased at the tibia in year 5: 17.4% ± 10% (p < 0.05), year 8: 55.2% ± 11% (p < 0.001), and year 12: 83.5% ± 14% (p < 0.001). A similar pattern of increase was observed at the radius. Failure load, which was higher than normal at baseline, decreased but remained above normal at year 12. This is the longest experience, to date, with PTH therapy in HypoPT. These results demonstrate sustained biochemical stability but overall decreases in bone mass. © 2023 American Society for Bone and Mineral Research (ASBMR).
Subject(s)
Calcium , Hypoparathyroidism , Humans , Parathyroid Hormone/pharmacology , Parathyroid Hormone/therapeutic use , Hypoparathyroidism/diagnostic imaging , Hypoparathyroidism/drug therapy , Bone and Bones , Bone Density , Absorptiometry, Photon , Vitamin D , Calcium, DietaryABSTRACT
Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is increasingly being diagnosed in the setting of evaluation for nephrolithiasis or metabolic bone diseases. It is important to demonstrate that PTH values remain consistently elevated and to measure ionized calcium levels to make the diagnosis. A diagnosis of normocalcemic disease is one of exclusion of secondary forms of hyperparathyroidism, including vitamin D deficiency, renal failure, medications, malabsorption, and hypercalciuria. Lack of rigorous diagnostic criteria and selection bias of the studied populations may explain the different rates of bone and renal complications. The natural history still remains unknown. Caution should be used in recommending surgery, unless clearly indicated. Here we will review the diagnostic features, epidemiology, clinical presentation, natural history, medical and surgical management of normocalcemic PHPT.
Subject(s)
Bone Diseases, Metabolic , Hyperparathyroidism, Primary , Vitamin D Deficiency , Humans , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/surgery , Hyperparathyroidism, Primary/complications , Parathyroid Hormone , Calcium , Vitamin D Deficiency/complicationsABSTRACT
ABSTRACT Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is increasingly being diagnosed in the setting of evaluation for nephrolithiasis or metabolic bone diseases. It is important to demonstrate that PTH values remain consistently elevated and to measure ionized calcium levels to make the diagnosis. A diagnosis of normocalcemic disease is one of exclusion of secondary forms of hyperparathyroidism, including vitamin D deficiency, renal failure, medications, malabsorption, and hypercalciuria. Lack of rigorous diagnostic criteria and selection bias of the studied populations may explain the different rates of bone and renal complications. The natural history still remains unknown. Caution should be used in recommending surgery, unless clearly indicated. Here we will review the diagnostic features, epidemiology, clinical presentation, natural history, medical and surgical management of normocalcemic PHPT.
ABSTRACT
Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Subject(s)
Hyperparathyroidism, Primary , Humans , Hyperparathyroidism, Primary/therapy , Systematic Reviews as Topic , Parathyroid HormoneABSTRACT
Approximately 1.5 million people in the United States currently identify as transgender. The use of gender affirming hormone therapy is integral to routine clinical care of transgender individuals, yet our understanding of the effects of this therapy is limited. There are reasons to believe that gender affirming hormone therapy may have important effects on cardiovascular risk and bone health in transgender individuals. The purpose of this review article is to summarize the evidence for the cardiovascular effects (including coronary artery disease, hypertension and stroke) as well as the effects on bone metabolism associated with gender affirming hormone therapy in both transgender men and transgender women.
ABSTRACT
Primary hyperparathyroidism is a common endocrine disorder. It used to present as a highly symptomatic disease before the advent of the multichannel autoanalyzer, now usually presenting as mild asymptomatic hypercalcemia. A newer presentation has been increasingly identified in the past two decades, normocalcemic primary hyperparathyroidism, presenting with elevated parathyroid hormone concentrations and consistently normal serum calcium. These patients are usually symptomatic, with parathyroid hormone levels measured in the evaluation for kidney stones or osteoporosis. It is important to exclude causes of secondary hyperparathyroidism. This review will focus on the evaluation and management of elevated parathyroid hormone levels in normocalcemic patients.
Subject(s)
Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/physiopathology , Calcium/blood , Humans , Hypercalciuria/epidemiology , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/epidemiology , Parathyroid Hormone/blood , Renal Insufficiency/epidemiology , Vitamin D Deficiency/epidemiologyABSTRACT
Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1-84) (rhPTH[1-84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1-84). The majority of patients (62%) took rhPTH(1-84) 100 µg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (-2.3% ± 0.8%) and ultradistal radius (-2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores -1.28 and - 1.69, respectively) and further declined at 48 months (-2.13 and - 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1-84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.
Subject(s)
Hypoparathyroidism , Absorptiometry, Photon , Adult , Bone Density , Bone and Bones , Female , Humans , Hypoparathyroidism/diagnostic imaging , Hypoparathyroidism/drug therapy , Male , Middle Aged , Radius , TibiaABSTRACT
CONTEXT: Conventional treatment of hypoparathyroidism is associated with decreased renal function and increased bone mineral density (BMD). OBJECTIVE: To evaluate the effects of 8 years of recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] therapy on key biochemical and densitometric indices. DESIGN: Prospective open-label trial. SETTING: Tertiary medical center. PARTICIPANTS: Twenty-four subjects with hypoparathyroidism. INTERVENTION: Treatment with rhPTH(1-84) for 8 years. MAIN OUTCOME MEASURES: Supplemental calcium and vitamin D requirements, serum calcium and phosphorus levels, calcium-phosphate product, urinary calcium excretion, estimated glomerular filtration rate (eGFR) and BMD. RESULTS: PTH therapy was associated with progressive reduction in supplemental calcium (57%; P < 0.01) and active vitamin D (76%; P < 0.001) requirements over 8 years. Serum calcium concentration was stable; urinary calcium excretion declined 38% (P < 0.01). eGFR remained stable and was related to baseline eGFR and serum calcium levels. Calcium-phosphate product was below the recommended limit; serum phosphorus remained within normal range. Lumbar spine and total hip BMD increased, peaking at 4 (mean ± SE, 4.6% ± 1.5%; P = 0.01) and 8 years (2.6% ± 1.1%; P = 0.02), whereas femoral neck BMD did not change and one-third radius BMD decreased (mean ± SE, -3.5% ± 1.1%; P = 0.001). BMD at all sites was higher throughout the 8 years than in the age- and sex-matched reference population. Hypercalcemia and hypocalcemia were uncommon. CONCLUSION: rhPTH(1-84) is a safe and effective treatment for hypoparathyroidism for 8 years. Long-term reductions in supplemental requirements and biochemical improvements with stable renal function are maintained.
Subject(s)
Hormone Replacement Therapy/methods , Hypoparathyroidism/drug therapy , Parathyroid Hormone/therapeutic use , Recombinant Proteins/therapeutic use , Adult , Aged , Calcium/blood , Female , Glomerular Filtration Rate/physiology , Hormone Replacement Therapy/adverse effects , Humans , Male , Middle Aged , Parathyroid Hormone/adverse effects , Parathyroid Hormone/blood , Phosphorus/blood , Prospective Studies , Recombinant Proteins/adverse effects , Treatment Outcome , Vitamin D/bloodABSTRACT
PURPOSE OF REVIEW: Hypoparathyroidism is a rare endocrine disorder characterized by low or insufficient parathyroid hormone (PTH) concentrations leading to hypocalcemia, hyperphosphatemia, and markedly reduced bone turnover. Despite being a rare disease, hypoparathyroidism has a profound impact on affected patients. RECENT FINDINGS: Recent epidemiologic surveys demonstrate a prevalence of between 5.3 and 40/100â000, confirming the orphan status of this disease. There is a female predominance, and anterior neck surgery is the most common etiology. Recent studies have better elucidated the chronic manifestations of the disease, impacting quality of life and multiple organ systems including the renal, cardiovascular, and skeletal systems. There are now data on longer term use of parathyroid hormone (PTH) and PTH analogs. SUMMARY: This review focuses on recent contributions to the literature on the prevalence and epidemiology of the disease, risk of chronic manifestations, and treatment with PTH(1-34) and rhPTH(1-84). Further research is needed to determine the pathophysiology of complications in hypoparathyroidism and whether interventions can decrease future risk of these complications. In addition, further data are needed with regards to more physiologic dosing regimens and long-term treatment with PTH and PTH analogs.
Subject(s)
Calcium/blood , Hypoparathyroidism/epidemiology , Parathyroid Hormone/blood , Protein Precursors/blood , Biomarkers/blood , Global Health , Humans , Hypoparathyroidism/blood , Prevalence , Quality of LifeABSTRACT
CONTEXT: Calcium and vitamin D treatment does not improve reduced quality of life (QOL) in hypoparathyroidism. Recombinant human (rh) PTH(1-84) therapy improves QOL metrics for up to 5 years. Data on QOL beyond this time point are not available. OBJECTIVES: To evaluate the effects of 8 years of rhPTH(1-84) therapy on QOL and factors associated with long-term benefit. DESIGN: Prospective, open-label trial. SETTING: Referral center. PATIENTS: Twenty patients with hypoparathyoidism. MAIN OUTCOME MEASURES: RAND 36-Item Short Form Health Survey (SF-36). RESULTS: rhPTH therapy led to substantial improvement in five of the eight SF-36 domains [vitality, social functioning (SF), mental health (MH), bodily pain (BP) and general health] and three of these domains (SF, MH, BP) were no longer lower than the reference population. The improvement in the mental component summary (MCS) score was sustained through 8 years, while the physical component summary (PCS) score improved through 6 years. A lower baseline QOL score was associated with greater improvement. A threshold value <238 (MCS) and <245 (PCS) predicted long-term improvement in 90% and 100% of the cohort, respectively. In patients whose calcium supplementation was reduced, MCS and PCS scores improved more than those whose supplementation did not decline to the same extent. Improvement in PCS was greater in patients whose calcitriol dosage was reduced and duration of disease was shorter. CONCLUSIONS: rhPTH(1-84) improves long-term well-being in hypoparathyroidism. The improvements are most prominent in those with impaired SF-36 at baseline and those whose requirements for conventional therapy decreased substantially.
Subject(s)
Calcium-Regulating Hormones and Agents/therapeutic use , Hypoparathyroidism/drug therapy , Parathyroid Hormone/therapeutic use , Quality of Life , Adult , Aged , Calcitriol/therapeutic use , Calcium/blood , Calcium/therapeutic use , Cholecalciferol/therapeutic use , Ergocalciferols/therapeutic use , Female , Humans , Hypoparathyroidism/blood , Hypoparathyroidism/physiopathology , Hypoparathyroidism/psychology , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Recombinant Proteins , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.
Subject(s)
Hyperparathyroidism, Primary , Bone Density , Calcium/blood , Humans , Hypercalcemia/diagnosis , Hypercalcemia/epidemiology , Hypercalcemia/etiology , Hypercalcemia/therapy , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/epidemiology , Hyperparathyroidism, Primary/therapy , Osteoporosis/complications , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Osteoporosis/therapy , Parathyroid Hormone/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/therapyABSTRACT
Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.
ABSTRACT
Hypoparathyroidism is associated with a spectrum of clinical manifestations in the acute and chronic settings, from mild to debilitating. Although the acute symptoms of hypocalcemia are primarily due to neuromuscular irritability, the chronic manifestations of hypoparathyroidism may be due to the disease itself or to complications of therapy or to both. The chronic complications of hypoparathyroidism can affect multiple organ systems, including the renal, neurologic, neuropsychiatric, skeletal, and immune systems. Further research is needed to determine the pathophysiology of complications in hypoparathyroidism and whether interventions can decrease the risk of these complications.
Subject(s)
Hypoparathyroidism/complications , Hypoparathyroidism/diagnosis , Calcinosis/etiology , Humans , Hypocalcemia/etiology , Hypoparathyroidism/therapyABSTRACT
Parathyroid hormone (PTH) (1-84) improves lumbar spine (LS) areal bone mineral density (aBMD) and trabecular bone score (TBS) in hypoparathyroidism over a 2-year treatment period. Studies in osteoporosis have shown that with PTH(1-34) there is a significant increase in LS aBMD and TBS. In this article, we provide new data comparing the effects of the same form of PTH, namely recombinant human PTH, rhPTH(1-84), on aBMD and TBS in hypoparathyroid and osteoporotic patients over an 18-month treatment period. We studied 19 premenopausal (mean age 45.8 ± 11.8 years) and 16 postmenopausal (71 ± 8.4 years) hypoparathyroid women and 38 women with postmenopausal osteoporosis (71 ± 8.3 years). DXA (hologic) at LS, femoral neck, total hip, and distal one-third radius was assessed. Site-matched LS TBS data were extracted from deidentified spine DXA scans using the TBS iNsight software (version 2.1; Medimaps, Geneva, Switzerland). We observed a significant increase in LS aBMD in premenopausal and postmenopausal hypoparathyroid (3 ± 1.1%, p < 0.02 and 3.1 ± 1.4%, p < 0.05, respectively) and osteoporosis (6.2 ± 1.1%, p < 0.0001) patients after 18 months. There was a significant increase (3 ± 1.5%, p = 0.05) in TBS in premenopausal hypoparathyroid patients. A change in TBS was not observed in either postmenopausal group. One-third radius aBMD significantly declined in postmenopausal hypoparathyroid (-3.6 ± 1.1%, p < 0.01) and osteoporosis (-8 ± 1.4%, p < 0.0001) patients. Overall, there was a significantly greater increase in TBS in premenopausal hypoparathyroid than in osteoporosis patients (p < 0.0001) after adjusting for baseline values, age, BMI, and average daily dose of rhPTH(1-84). Comparing only postmenopausal women, the LS aBMD increase was greater in osteoporotic than hypoparathyroid subjects (p < 0.01). Our results demonstrate that rhPTH(1-84) administered for 18 months increases trabecular aBMD in hypoparathyroidism and postmenopausal osteoporosis with greater gains observed in the subjects with osteoporosis. The data suggest different effects of PTH on bone depending on the baseline skeletal structure, skeletal dynamics, compartments, and menopausal status. © 2018 American Society for Bone and Mineral Research.
Subject(s)
Bone Density , Cancellous Bone/pathology , Hypoparathyroidism/drug therapy , Hypoparathyroidism/physiopathology , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/physiopathology , Parathyroid Hormone/therapeutic use , Recombinant Proteins/therapeutic use , Bone Density/drug effects , Cancellous Bone/drug effects , Cancellous Bone/physiopathology , Female , Humans , Hypoparathyroidism/pathology , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/pathology , Lumbar Vertebrae/physiopathology , Middle Aged , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/pathology , Parathyroid Hormone/pharmacology , Recombinant Proteins/pharmacologyABSTRACT
Hypoparathyroidism is a rare disorder that is associated with abnormal bone properties. Recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] in short-term studies has beneficial skeletal effects. Although rhPTH(1-84) will likely be used indefinitely, long-term effects on skeletal microstructure are unknown. We therefore studied histomorphometric changes with transiliac crest bone biopsies before and after 8.3 ± 1 years of rhPTH(1-84) in 13 hypoparathyroid subjects compared with 45 controls. Before institution of rhPTH(1-84), skeletal remodeling indices were markedly suppressed. With long-term treatment, indices of bone remodeling increased. Mineralizing surface increased by 26-fold (0.3 ± 1 to 7.9 ± 7%, p = 0.003), bone formation rate increased by 15-fold (0.003 ± 0.01 to 0.047 ± 0.05 µm2 /µm/day, p = 0.007), osteoid width doubled (1.9 ± 1 to 4.3 ± 1 lamellae, p = 0.017), and osteoid surface tripled (3.3 ± 3 to 10.8 ± 6%, p = 0.011). Bone resorption as measured by eroded surface increased (4.6 ± 2 to 7.5 ± 3%, p = 0.021). Structural changes demonstrated intratrabecular tunneling, with increases in cancellous bone volume (19.6 ± 5 to 29.1 ± 11%, p = 0.017) and trabecular number (1.8 ± 1 to 2.5 ± 1 #/mm, p = 0.025). Cortical porosity tended to increase (6.3 ± 5 to 9.5 ± 3%, p = 0.07). Mineralizing surface, osteoid surface, and eroded surface surpassed control levels, as did cancellous bone volume, trabecular number, and cortical porosity. These data, the first to reflect such long exposure of any PTH for any disease, illustrate that PTH establishes and maintains a new skeletal state for at least 8 years in hypoparathyroidism. © 2018 American Society for Bone and Mineral Research.
Subject(s)
Bone and Bones/pathology , Hypoparathyroidism/drug therapy , Parathyroid Hormone/administration & dosage , Parathyroid Hormone/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Adult , Aged , Case-Control Studies , Cohort Studies , Female , Humans , Male , Middle Aged , Parathyroid Hormone/pharmacology , Recombinant Proteins/pharmacology , Time FactorsABSTRACT
Context: Obesity has been shown to be unfavorable to skeletal microarchitecture when assessed by trabecular bone score (TBS). The influence of adiposity on skeletal microstructure in primary hyperparathyroidism (PHPT) has not yet been evaluated. Objective: To investigate the effect of obesity on TBS and bone mineral density (BMD) in subjects with PHPT at baseline and through 2 years after parathyroidectomy. Design: Prospective observational study. Setting: Referral center. Patients or Other Participants: Thirty men and women with PHPT undergoing parathyroid surgery. Main Outcome Measures: TBS and BMD by dual-energy X-ray absorptiometry (DXA). Results: There were notable improvements in lumbar spine and femoral neck BMD in the obese (lumbar spine: 4.3 ± 4.7%, femoral neck: 3.8 ± 6.6%; P < 0.05 for both) and nonobese subjects (lumbar spine: 3.8 ± 5.6%, femoral neck 3.1 ± 5.0%; P < 0.05 for both) but no marked change in TBS in either group at 24 months postparathyroidectomy. Obese subjects had fully degraded TBS values compared with the nonobese subjects, whose TBS values were minimally below normal throughout the study (baseline: 1.199 ± 0.086 vs 1.327 ± 0.099, respectively; P = 0.003; 24 months: 1.181 ± 0.061 vs 1.352 ± 0.114, respectively; P = 0.001), despite improvements in BMD. Conclusions: The detrimental effect of obesity on TBS, an index of bone quality, was demonstrated in subjects with PHPT. Obesity was associated with fully degraded skeletal microarchitecture as measured by TBS in PHPT, despite similar values in bone density by DXA compared with nonobese subjects. TBS values did not improve postparathyroidectomy in either obese or nonobese subjects.
Subject(s)
Cancellous Bone/diagnostic imaging , Hyperparathyroidism, Primary/diagnostic imaging , Obesity/diagnostic imaging , Parathyroidectomy , Absorptiometry, Photon , Aged , Bone Density/physiology , Female , Humans , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/surgery , Male , Middle Aged , Obesity/complications , Treatment OutcomeABSTRACT
Traditional hypercalcemic primary hyperparathyroidism is a common endocrine disease. Patients with a history of nephrolithiasis or a suspected metabolic bone disease are increasingly being identified with elevated PTH concentrations in the setting of consistently normal serum and ionized calcium concentrations. In the absence of secondary causes of hyperparathyroidism, a diagnosis of normocalcemic primary hyperparathyroidism is reasonable. As most cohorts described in the literature are from referral populations, involvement of the skeleton and the kidneys is common, two traditional target organs of primary hyperparathyroidism. Data from small cohorts show patients with normocalcemic disease respond similarly to hypercalcemic primary hyperparathyroidism with regard to medical and surgical approaches. In normocalcemic patients, multiglandular disease may be more common. In this article, we review the available literature on the epidemiology, diagnosis, clinical features, medical and surgical management of this newer phenotype of primary hyperparathyroidism.
Subject(s)
Hyperparathyroidism, Primary/therapy , Calcium/blood , Humans , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/epidemiology , Kidney Calculi/etiology , Kidney Calculi/therapy , Parathyroid Hormone/blood , PhenotypeABSTRACT
Context: High-resolution peripheral quantitative computed tomography (HRpQCT) is a noninvasive imaging technology that can provide insight into skeletal microstructure and strength. In asymptomatic primary hyperparathyroidism (PHPT), HRpQCT imaging has demonstrated both decreased cortical and trabecular indices, consistent with evidence for increased fracture risk. There are limited data regarding changes in HRpQCT parameters postparathyroidectomy. Objective: To evaluate changes in skeletal microstructure by HRpQCT in subjects with PHPT after parathyroidectomy. Design: We studied 29 subjects with PHPT (21 women, 8 men) with HRpQCT at baseline and 6, 12, 18, and 24 months postparathyroidectomy. Main Outcome Measures: Volumetric bone mineral density, microarchitectural indices, and finite element analysis at the distal radius and tibia. Results: At both the radius and tibia, there were significant improvements in total, cortical, and trabecular volumetric bone density as early as 6 months postparathyroidectomy (24-month values for total volumetric bone density, radius: +2.8 ± 4%, tibia: +4.4 ± 4%; P < 0.0001 for both), cortical thickness (radius: +1.1 ± 2%, tibia: +2.0 ± 3%; P < 0.01 for both), and trabecular bone volume (radius: +3.8 ± 5%, tibia: +3.2 ± 4%; P < 0.0001 for both). At both sites, by finite element analysis, stiffness and failure load were improved starting at 6 months postparathyroidectomy (24-month values for failure load, radius: +6.2 ± 6%, tibia: +4.8 ± 7%; P < 0.0001 for both). Conclusions: These results provide information about skeletal microarchitecture in subjects with PHPT followed through 2 years after parathyroidectomy. Estimated bone strength is improved, consistent with data showing decreased fracture risk postparathyroidectomy.