Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies

The dual face of parathyroid hormone and prostaglandins in the osteoimmune system

“…Bone microenvironment is characterized by the elegant poise between osteoblasts and osteoclasts in a multifaceted bone remodeling process which occurs predominantly at the cancelous and endosteal surfaces in close proximity to the bone marrow. The current findings concur that osteoblasts are recruited in distinct areas called "basic multicellular units" by osteoclasts via cross-talk between both cell types and begin to lay down new bone matrixes (14,25). This complex and dynamic equilibrium of bone cells is regulated by several systemic factors, such as bone morphogenetic proteins (68,97,102,146), parathyroid hormone (PTH) (39,73,100), and prostaglandins (PGs) (3,4,99,101), as well as shared cytokines, transcription factors, and membrane receptors in the immune and skeletal systems (49,123).…”

“…In line with this, continuous PTH infusion in rodents decreased bone mass by enhancing trabecular bone loss and endosteal resorption through stimulation of osteoclast formation and activity (19,43,81). Furthermore, the bone anabolism induced by intermittent PTH administration stopped after 1-2 yr, and the treatment protocols for osteoporosis with recombinant human PTH are currently limited to 18 -24 mo (25). The catabolic effect produced by PTH is mediated in part by the increased production of RANKL and M-CSF coupled with the decreased production of OPG by stromal cells and osteoblasts (35,61,138).…”

Intermittent PTHrP(1–34) Exposure Augments Chondrogenesis and Reduces Hypertrophy of Mesenchymal Stromal Cells

“…Interestingly, PTH can exert opposing effects on the osteogenic differentiation of osteoblasts [19,20], rat MSCs [21], and on bone mass dependent on a constant versus intermittent application regime. Whereas constant application acted catabolically on bone, an intermittent application (eg, once daily) provided anabolic effects, resulting in a net increase in bone mass [22,23]. Similar effects were reported for PTHrP [24][25][26] and first clinical trials are conducted to evaluate the benefit of intermittent PTHrP administration for the treatment of osteoporosis [27].…”

Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin–glutaraldehyde biopolymer-coated hydroxyapatite

“…In fact, these agents (now represented mainly by bone morphogenetic proteins) comprise about 20% of the whole orthopaedic market in the US -a 3-fold higher figure than the current percentage of resorbable implants -and this percentage is expected to grow rapidly [14]. An emerging factor in this regard is parathyroid hormone-related protein (PTHrP), the N-terminal fragment of which has been shown to induce bone anabolic actions in rodents and humans upon systemic daily administration [15,16]. In addition, the C-terminal 107-111 domain (also known as osteostatin) of PTHrP also exhibits osteogenic features in vitro, and stimulates bone accrual in vivo [17][18][19][20][21][22][23][24][25].…”