In hypoparathyroidism, plasma parathyroid hormone (PTH) levels are inadequate to maintain plasma calcium concentration within the reference range. On conventional treatment with calcium supplements and active vitamin D analogues, bone turnover is abnormally low, and BMD is markedly increased. We aimed to study the effects of PTH-replacement therapy (PTH-RT) on calciumphosphate homeostasis and BMD. In a double-blind design, we randomized 62 patients with hypoparathyroidism to daily treatment with PTH(1-84) 100 mg or similar placebo for 24 weeks as add-on therapy to conventional treatment. Compared with placebo, patients on PTH(1-84) reduced their daily dose of calcium and active vitamin D significantly by 75% and 73%, respectively, without developing hypocalcemia. However, hypercalcemia occurred frequently during the downtitration of calcium and active vitamin D. Plasma phosphate and renal calcium and phosphate excretion did not change. Compared with placebo, PTH(1-84) treatment significantly increased plasma levels of bone-specific alkaline phosphatase (þ226% AE 36%), osteocalcin (þ807% AE 186%), N-terminal propeptide of procollagen 1 (P1NP; þ1315% AE 330%), cross-linked C-telopeptide of type 1 collagen (CTX; þ1209% AE 459%), and urinary cross-linked N-telopeptide of type 1 collagen (NTX; (þ830% AE 165%), whereas BMD decreased at the hip (À1.59% AE 0.57%), lumbar spine (À1.76% AE 1.03%), and whole body (À1.26% AE 0.49%) but not at the forearm. In conclusion, the need for calcium and active vitamin D is reduced significantly during PTH-RT, whereas plasma calcium and phosphate levels are maintained within the physiologic range. In contrast to the effect of PTH(1-84) treatment in patients with osteoporosis, PTH-RT in hypoparathyroidism causes a decrease in BMD. This is most likely due to the marked increased bone turnover. Accordingly, PTH-RT counteracts the state of overmineralized bone and, during long-term treatment, may cause a more physiologic bone metabolism. ß

No abstract

It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on these respective surfaces, and that bone formation occurs only above a given cell density. Canopies appeared an important source of osteoprogenitors, because (i) canopy cells proved to be more proliferative and less differentiated than bone surface cells, as shown by the inverse levels of Ki-67 and procollagen-3 N-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope surrounding the red bone marrow, which is lifted and hypertrophied on initiation of bone resorption. This study, together with earlier reports, led to a model in which canopies and nearby capillaries are critical for reaching the osteoblast density required for bone formation.

Overall, our data do not support an immediate beneficial effect of PTH replacement therapy on muscle function or QoL. A high frequency of hypercalcemia among our patients may have compromised the potential beneficial effects of reversing the state of PTH insufficiency.

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoTþPT) as compared to patients with postsurgical HypoT and healthy controls. Age-and gender-matched patients on treatment for HypoTþPT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoTþPT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoTþPT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoTþPT, but not in HypoT. In HypoTþPT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoTþPT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoTþPT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoTþPT patients are warranted.