Treatment of osteoporosis with parathyroid hormone: evidence and perspective

Parathyroid hormone (PTH) is a promising bone formation-stimulating agent, and the recent large-scale randomized controlled trial (RCT) revealed that parathyroid hormone increases and reduces lumbar bone mineral density and fracture risk, respectively, more potently than bisphosphonates. Moreover, PTH is also effective for male or glucocorticoid-induced osteoporosis. However, the recent studies showed that the co administration of PTH and bisphosphonate is not good. The further accumulation of evidence about the combined or subsequent therapy is expected.     

Risk for osteoporosis and fracture with glucocorticoids

Glucocorticoid use is ubiquitous and is associated with multiple adverse reactions. Among them, osteoporosis and bone fractures are of our concern. In this review, we present current evidence on the effect of glucocorticoids on bone mineral density and the risk of fractures, the mechanisms underlying those effects, and the recommendations for monitoring and treating patients who take them.The bone mineral density of the lumbar spine and total hip is lower, and the risk of fractures is higher in glucocorticoid users than non-users. These effects have a rapid onset, are dose-dependent, and improve soon after discontinuation of glucocorticoids. They also appear to occur even with non-systemic routes of administration and with low doses.Glucocorticoids reduce bone mineral density by increasing osteoclast activity and decreasing osteoblast and osteocyte activity. Calcium metabolism and parathyroid hormone activity are less important than was initially thought.Treatment decisions are on risk stratification using clinical, radiographic, and prediction tools. Our armamentarium for the treatment and prevention of glucocorticoid-induced osteoporosis includes calcium and vitamin D, bisphosphonates, recombinant parathyroid hormone, monoclonal antibodies against receptor activator of nuclear factor kappa-B ligand, and hormone treatments.     

The use of parathyroid hormone in the treatment of osteoporosis

Anabolic skeletal agents have recently broadened our therapeutic options for osteoporosis. By directly stimulating bone formation, they reduce fracture incidence by improving bone qualities in addition to increasing bone mass. Teriparatide [recombinant human parathyroid hormone(1–34)], the only anabolic agent currently approved in the United States for osteoporosis, has emerged as a major therapeutic approach to selected patients with osteoporosis. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. With the use of this anabolic agent, bone density and bone turnover increase, microarchitecture improves, and bone size is beneficially altered. The incidence of vertebral and nonvertebral fractures is reduced with teriparatide use. Combination therapy with parathyroid hormone and an antiresorptive does not appear to offer definitive advantages over the use of PTH or an antiresorptive alone, although recent ideas about combining these agents may offer new insights. In order to maintain increases in bone density acquired during PTH therapy, it is important to follow its use with an antiresorptive agent.     

Parathyroid hormone

Parathyroid hormone (PTH) is the most recently approved agent for osteoposis treatment. It differs from other therapies that act by inhibiting bone resorption, because it stimulates bone formation. The resultant increases in bone mineral density are therefore greater than those associated with therapy with bisphosphonates (BPs), selective estrogen receptor modulators, or calcitonin. Despite being available for at least 2 yr. PTH has not been exten sively studied. Although some existing data support its use for reducing the risk of vertebral fractures in women. data are still limited with regard to nonvertebral fracture prevention in women and fracture prevention in men. Preliminary studies have demonstrated a potential role in the management of patients with glucocorticoid-induced osteoporosis, but more data are needed. PTH is administered daily by subcutaneous injection for a maximum of 24 mo. Common adverse effects include pain with injection, arthralgia, and nausea. PTH caused an increase in osteosarcoma in rats and therefore, its use should be avoided in patients at increased risk of osteosarcoma, such as those with Paget's disease, unexplained baseline elevations of alkaline phosphatase, open epiphyses, or previous skeletal radiation exposure. At this time. PTH should not be combined with other agents, but a 2-yr treatment period may be sequentially followed by a BP. Because of high cost, the need for parenteral administration and potential for adverse effects, PTH use should be reserved for patients with severe osteoporosis who fail BP therapy.     

PTH-analogs: Comparable or different?

Because no comparative studies exist, no clear pronouncements can be made about the potential differences in effectiveness and safety between PTH 1–34 and PTH 1–84. As regards the efficacy, a convincing reduction of vertebral fractures was shown in both cases [Neer, R.M., Arnaud, C.D., Zanchetta, J.R., Prince, R., Gaich, G.A., Reginster, J.Y., Hodsman, A.B., Eriksen, E.F., Ish-Shalom, S., Genant, H.K., Wang, O., Mitlak, B.H., 2001. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434–1441; Greenspan, S.L., Bone, H.G., Ettinger, M.P., Hanley, D.A., Lindsay, R., Zanchetta, J.R., Blosch, C.M., Mathisen, A.L., Morris, S.A., Marriott, T.B., Treatment of Osteoporosis with Parathyroid Hormone Study Group, 2007. Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann. Intern. Med. 146, 326–339]. A reduction of non-vertebral fractures was shown in the case of PTH 1–34 only. Another significant resemblance is that both medicines have a strong anabolic action; this mechanism of action is essentially different from the bisphosphonates and strontium ranelate. Both medicines constitute a welcome addition to the therapeutic arsenal for patients with severe osteoporosis. More data from literature (including information on follow-up data and use in men) are available for PTH 1–34 because it has been available for longer. As regards the side effect profile, PTH 1–84 appears to have a higher incidence of hypercalcemia, hypercalciuria and nausea than teriparatide. Here, too, no comparative study exists: the differences may therefore be based on an actual difference in side effects, or it may be ascribed to differences in definitions and/or patient populations.     

Treatment of osteoporosis and Paget's disease

Osteoporosis is a major public health problem. In women, the estimated lifetime risks of hip and vertebral fractures are 15% and 25%, respectively. The development of accurate and reproducible methods of assessing bone mineral density has enabled identification of persons at risk of fracture and assessment of response to treatment. Estrogen replacement therapy is effective in the prophylaxis of postmenopausal osteoporosis, and is the only therapy with well-proven antifracture efficacy. Fluoride can dramatically increase bone density, although a recent large, controlled study has demonstrated no effect on vertebral fractures. Bisphosphonates are emerging as a likely effective therapy for both idiopathic and glucocorticoid-induced osteoporosis. Calcium, vitamin D, calcitonin, and anabolic steroids may still have a role. Parathyroid hormone is a promising development that will need further study. Paget's disease is also common, affecting more than 3% of people over 40 years old. Calcitonin is an established therapy, although the bisphosphonates are a promising alternative.     

Quantitative computed tomography of the lumbar spine,not dual x-ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3).CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.     

Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study

PURPOSE: To assess the comparative effectiveness of several medications on bone mineral density, biochemical bone markers, and the incidence of vertebral fractures in postmenopausal women with osteoporosis. METHODS: A total of 396 postmenopausal women, aged 50 to 75 years, were allocated randomly to six equal-sized groups: hormone replacement therapy, etidronate, eel calcitonin, alfacalcidol, vitamin K (menatetrenone), or control (no treatment). Thoracic and lumbar spine radiographs, bone mineral density at the distal radius, and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study. RESULTS: Compared with baseline, the 2-year mean changes in bone mineral density were 2.0% for hormone replacement therapy, -0.5% for etidronate, 1.6% for calcitonin, -3.6% for alfacalcidol, -1.9% for vitamin K, and -3.3% for control. Seventeen (26%) of the 66 control patients developed new vertebral fractures. Compared with controls, the relative risks of vertebral fracture were 0.35 (95% confidence interval [CI]: 0.14 to 0.83) for hormone replacement therapy, 0.40 (95% CI: 0.17 to 0.92) for etidronate, 0.41 (95% CI: 0.17 to 0.93) for calcitonin, 0.56 (95% CI: 0.26 to 1.12) for alfacalcidol, and 0.44 (95% CI: 0.20 to 0.99) for vitamin K. CONCLUSION: We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy, etidronate, and calcitonin, and significant improvements in bone mineral density with hormone replacement therapy and calcitonin.     

Anabolic Agents for Osteoporosis

Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving other bone qualities in addition to increasing bone mass. Teriparatide (human parathyroid hormone[1-34]) has clearly emerged as a major approach for selected patients with osteoporosis. Teriparatide increases bone mineral density and bone turnover, improves bone microarchitecture, and changes bone size. The incidence of vertebral and non-vertebral fractures is reduced. Teriparatide is approved in many countries throughout the world for the treatment of both postmenopausal women and men with osteoporosis who are at high risk for fracture. Another anabolic agent, strontium ranelate, may both promote bone formation and inhibit bone resorption. Clinical trials support the use of strontium ranelate as a treatment for postmenopausal osteoporosis and have shown that strontium ranelate reduces the frequency of vertebral and non-vertebral fractures. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, growth hormone, and insulin-like growth factor-I, have been examined, although less data are currently available on these approaches.     

Alcohol-Induced Bone Disease: Relationship to Age and Parathyroid Hormone Levels

Alcohol abuse leads to osteopenia and fractures. Epidemiological evidence suggests that older alcoholics are at substantially greater risk of fractures than younger alcoholics. To examine the interaction of age and alcohol abuse on bone mineral homeostasis, we studied 27 subjects with a history of 10 or more years of alcohol abuse ranging in age from 26–68 years. They were evaluated for disordered bone mineral homeostasis by assessing bone density (by quantitative computed tomography of the lumbar spine), histomorphometry of a transcortical biopsy from the iliac crest, serum levels of vitamin D metabolites and parathyroid hormone, and serum and urine levels of bone minerals. Seventeen of the subjects were found to have spinal compression fractures by routine radiologic procedures. The older the subject the more likely the subject was to have such a fracture. Bone densitometry indicated a marked reduction in spinal bone density with 15 subjects below 2 SD of normal aged-matched controls. Bone density fell sharply with the age of the subject. Histomorphometry of iliac crest bone biopsies revealed no evidence of osteomalacia, but total resorption surfaces were increased. Consistent with the lack of osteomalacia were the normal levels of the vitamin D metabolites. The increased total resorption surfaces were correlated with high normal or elevated levels of parathyroid hormone as indicated both by radioimmunoassay and by urinary cAMP levels. Bone formation and active bone resorption (resorption surfaces containing osteoclasts) did not correlate with parathyroid hormone levels, however, but correlated negatively with age. Younger alcoholics tended to have increased bone remodeling, whereas older alcoholics tended to have suppressed bone remodeling out of proportion to the normal decline with age. We conclude that parathyroid hormone may play a role in stimulating bone resorption in younger alcoholics. With time the cumulative effects of alcohol abuse result in reduced bone resorption, as well as reduced bone formation, regardless of the levels of parathyroid hormone, ultimately leading to osteoporosis.     

Bone mineral density in primary hyperparathyroidism

Skeletal complications of advanced hyperparathyroidism include clinically bone pains, muscle weakness, bone deformities and fractures. X-ray studies reveal subperiosteal bone resorption, atrophy of the cortex of long bones, cysts, brown tumours and calcifications of soft tissues; these changes appear in the late period of the disease. In recent onset of hyperparathyroidism bone changes may be detected by X-ray absorptiometry. Thus the aim of our study was to evaluate bone mineral density with the use of dual energy X-ray absorptiometry (DEXA) at two sites: in lumbar vertebral bodies consisting mainly of the trabecular bone and in 1/3 distal part of the radius composed predominantly of the cortical bone. Twenty-three patients with primary hyperparathyroidism were included in our study. Hypercalcemia (ionized calcium above 5.4 mg/100 ml, total calcium above 10.6 mg/100 ml) and increased serum PTH, above 100 pg/ml, were detected in all patients. Isotope scintigraphy using 99mTc-MIBI revealed the presence of a parathyroid adenoma; this was confirmed at surgery and histopathologically. In bone densitometry we found greatly reduced bone mineral density (BMD) in 1/3 distal part of the radius amounting to 66.8 +/- 12.0% of the age-matched range and markedly smaller bone loss in lumbar spine, BMD was 91.7 +/- 14.6%. In 10 patients control densitometry, performed 6-24 months after parathyroid adenomectomy, revealed a marked 10 to 22% increase in bone density of lumbar vertebral bodies in the first year. BMD of the 1/3 distal part of the radius increased to a smaller degree 6.3% per year. CONCLUSIONS: 1. Bone densitometry in primary hyperparathyroidism reveals pronounced decrease in bone mineral density in the 1/3 distal part of the radius and much smaller decrease of the lumbar spine density. 2. Parathyroid adenomectomy leads to a rapid increase in density of the trabecular bone L1-L4 vertebral bodies and much smaller increase in the cortical bone of the radius. 3. Pronounced differences in bone mineral density of cortical bone and trabecular bone surpassing 20% are characteristic of hyperparathyroidism as they do not occur in other types of osteoporosis.     

Fracture thresholds in osteoporosis: implications for hormone replacement treatment.

The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.     

Treatment of postmenopausal osteoporosis

The aim of treatment of postmenopausal osteoporosis is to reduce the frequency of vertebral and non-vertebral fractures (especially at the hip), which are responsible for morbidity associated with the disease. Results of large placebo controlled trials have shown that alendronate, raloxifene, risedronate, the 1-34 fragment of parathyroid hormone, and nasal calcitonin, greatly reduce the risk of vertebral fractures. Furthermore, a large reduction of non-vertebral fractures has been shown for alendronate, risedronate, and the 1-34 fragment of parathyroid hormone. Calcium and vitamin D supplementation is not sufficient to treat individuals with osteoporosis but is useful, especially in elderly women in care homes. Hormone replacement therapy remains a valuable option for the prevention of osteoporosis in early postmenopausal women. Choice of treatment depends on age, the presence or absence of prevalent fractures, especially at the spine, and the degree of bone mineral density measured at the spine and hip. Non-pharmacological interventions include adequate calcium intake and diet, selected exercise programmes, reduction of other risk factors for osteoporotic fractures, and reduction of the risk of falls in elderly individuals.     

Postmenopausal bone loss at multiple skeletal sites: relationship to estrogen use

Bone mineral content (BMC) was measured in the distal radius, proximal radius, and os calcis in 608 postmenopausal women, and the values were compared to vertebral osteoporosis and compression fractures determined radiographically, as well as to history of estrogen use. Current estrogen users had significantly higher BMC at all appendicular sites as compared to non-users. Prior estrogen users had lower appendicular BMC's than current users, but they were still significantly higher than non-users. However, radiographic assessment of the lumbar spine showed no difference in osteoporosis or compression fracture prevalence between prior users and non-users of estrogen, whereas current estrogen users had a significantly lower prevalence of osteoporosis in the spine. These findings suggest that estrogen effect on trabecular bone in the os calcis may be more transient than on cortical, appendicular bone. They also suggest that long term or permanent estrogen replacement is required to prevent spinal compression fractures.     

A study of male patients with forearm fracture in Northern Ireland

Osteoporosis, although considered less common, still occurs in men. We present a cross-sectional study of a group of Northern Ireland men with low-trauma forearm fractures to determine the presence of osteoporosis and screen for secondary causes of low bone mineral density. Male patients aged 30–75 years, presenting with distal forearm fracture in 2000–2001 in Northern Ireland, were identified through a Colles fracture database. A total of 37 subjects consented to have bone mineral density measurements undertaken at the femoral neck, spine and forearm using a Lunar expert bone densitometer. Twenty-seven percent of the men had osteoporosis at the spine, femoral neck or forearm, as defined by a bone mineral density score of less than −2.5. We also found that 49% of patients had vitamin D insufficiency or deficiency, 27% had low serum testosterone, 14% had abnormal liver function test results, and 14% had raised parathyroid hormone. Only one patient received advice or treatment regarding osteoporosis at the time of fracture. Increased awareness of male osteoporosis and the need for screening for potential secondary causes in this group of patients is required, both at primary and secondary care level.     

Enhancement of fracture healing with parathyroid hormone

Since the approval of parathyroid hormone (PTH) as an anabolic treatment for osteoporosis, there has been an increasing interest in other potential clinical uses for this compound in musculoskeletal conditions. Fracture healing is one area of particular interest. It is now widely recognized that daily PTH administration is an effective therapy for increasing bone mineral density and preventing fractures in both male and female osteoporosis patients. More recently, a growing body of evidence supports the conclusion that PTH will also be an effective anabolic therapy for the enhancement of bone repair following fracture. Several animal studies have demonstrated that PTH therapy consisting of daily subcutaneous injections during repair leads to increased callus volumes and a more rapid return of bone strength. Additionally PTH, these reports demonstrated that PTH treatment enhanced repair in older animals, models of osteoporosis, and healthy sexually mature animals. These results underscore the potential of PTH as an anabolic therapy for enhancing the rate of bone repair and regain of mechanical strength in a broad spectrum of fracture patients.     

Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures

Glucocorticoids are the most common cause of drug-related osteoporosis. We reviewed current evidence on risk factors for glucocorticoid-induced osteoporosis (GIOP) and prevention and treatment of GIOP-related fractures. Guidelines for GIOP management published since 2000 were also reviewed. Significant bone loss and increased fracture risk is seen with daily prednisone doses as low as 5 mg. Alternate-day glucocorticoid therapy can lead to similar bone loss. No conclusive evidence exists for a safe minimum dose or duration of glucocorticoid exposure. Physicians should consider risk factors for involutional osteoporosis such as older age, postmenopausal status, and baseline bone density measurements as they assess patients for prevention or treatment of GIOP. Bisphosphonates were reported to reduce GIOP-related vertebral fractures, but inconclusive data exist for hip fractures associated with glucocorticoid use. Hormone replacement therapy and parathyroid hormone analogs are effective in preserving bone density in GIOP. The risk of osteoporosis and fractures should be routinely assessed in patients receiving glucocorticoid therapy. Effective prevention and treatment options are available and can result in meaningful reduction of GIOP-related morbidity and mortality. Current guidelines for GIOP management recommend bisphosphonates, especially alendronate and risedronate, as first-line agents for GIOP, and these guidelines propose the preventive use of bisphosphonates early in the course of glucocorticoid therapy in high-risk patient subgroups.     

Serum levels of intact parathyroid hormone and alkaline phosphatase correlate with cortical and trabecular bone loss in primary hyperparathyroidism.

We examined the relationship between bone loss and several biochemical indices in 38 patients with primary hyperparathyroidism. Bone mineral density was reduced by 12 +/- 4.0% in the lumbar spine, 18 +/- 4.2% at the distal radius and 21 +/- 2.8% at the proximal radius (mean +/- SEM). There were significant negative correlations between the serum concentrations of intact parathyroid hormone (PTH) and the Z-scores of the bone mineral content at the proximal and distal radius. In the lumbar spine, bone mineral density was greater in patients with mildly elevated PTH and less in patients whose PTH levels exceeded 8.6 pmol/l. We also observed a strong association between increased levels of serum alkaline phosphatase and low bone mineral Z-scores. Our data thus indicate that cortical and, with the exception of mild primary hyperparathyroidism, trabecular bone loss is proportional to the concentration of circulating PTH and the severity of PTH-induced bone turnover. For the individual patient, however, the usefulness of intact PTH and alkaline phosphatase measurements for assessing bone loss associated with primary hyperparathyroidism seems to be only limited.     

The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism

BACKGROUND AND OBJECTIVE: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients. METHODS: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects. RESULTS: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm(2)): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group. CONCLUSIONS: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.